Posttransplant complications: molecular mechanisms and therapeutic interventions

Xiaoyou Liu , Junyi Shen , Hongyan Yan , Jianmin Hu , Guorong Liao , Ding Liu , Song Zhou , Jie Zhang , Jun Liao , Zefeng Guo , Yuzhu Li , Siqiang Yang , Shichao Li , Hua Chen , Ying Guo , Min Li , Lipei Fan , Liuyang Li , Peng Luo , Ming Zhao , Yongguang Liu

MedComm ›› 2024, Vol. 5 ›› Issue (9) : e669

PDF
MedComm ›› 2024, Vol. 5 ›› Issue (9) : e669 DOI: 10.1002/mco2.669
REVIEW

Posttransplant complications: molecular mechanisms and therapeutic interventions

Author information +
History +
PDF

Abstract

Posttransplantation complications pose a major challenge to the long-term survival and quality of life of organ transplant recipients. These complications encompass immune-mediated complications, infectious complications, metabolic complications, and malignancies, with each type influenced by various risk factors and pathological mechanisms. The molecular mechanisms underlying posttransplantation complications involve a complex interplay of immunological, metabolic, and oncogenic processes, including innate and adaptive immune activation, immunosuppressant side effects, and viral reactivation. Here, we provide a comprehensive overview of the clinical features, risk factors, and molecular mechanisms of major posttransplantation complications. We systematically summarize the current understanding of the immunological basis of allograft rejection and graft-versus-host disease, the metabolic dysregulation associated with immunosuppressive agents, and the role of oncogenic viruses in posttransplantation malignancies. Furthermore, we discuss potential prevention and intervention strategies based on these mechanistic insights, highlighting the importance of optimizing immunosuppressive regimens, enhancing infection prophylaxis, and implementing targeted therapies. We also emphasize the need for future research to develop individualized complication control strategies under the guidance of precision medicine, ultimately improving the prognosis and quality of life of transplant recipients.

Keywords

infection / malignancy / organ transplantation / posttransplant complications / rejection / T cell

Cite this article

Download citation ▾
Xiaoyou Liu, Junyi Shen, Hongyan Yan, Jianmin Hu, Guorong Liao, Ding Liu, Song Zhou, Jie Zhang, Jun Liao, Zefeng Guo, Yuzhu Li, Siqiang Yang, Shichao Li, Hua Chen, Ying Guo, Min Li, Lipei Fan, Liuyang Li, Peng Luo, Ming Zhao, Yongguang Liu. Posttransplant complications: molecular mechanisms and therapeutic interventions. MedComm, 2024, 5(9): e669 DOI:10.1002/mco2.669

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Datta RR, Schran S, Persa OD, et al. Post-transplant malignancies show reduced T-cell abundance and tertiary lymphoid structures as correlates of impaired cancer immunosurveillance. Clin Cancer Res. 2022; 28(8): 1712-1723.

[2]

Grinyó JM. Why is organ transplantation clinically important? Cold Spring Harb Perspect Med. 2013; 3(6).

[3]

Conrad SA, Chhabra A, Vay D. Long-term follow-up and complications after cardiac transplantation. J La State Med Soc. 1993; 145(5): 217-220. 223–5.

[4]

Sen A, Callisen H, Libricz S, Patel B. Complications of solid organ transplantation: cardiovascular, neurologic, renal, and gastrointestinal. Crit Care Clin. 2019; 35(1): 169-186.

[5]

Li Q, Lan P. Activation of immune signals during organ transplantation. Signal Transduct Target Ther. 2023; 8(1): 110.

[6]

Fishman JA. Infection in organ transplantation. Am J Transplant. 2017; 17(4): 856-879.

[7]

Shivaswamy V, Boerner B, Larsen J. Post-transplant diabetes mellitus: causes, treatment, and impact on outcomes. Endocr Rev. 2016; 37(1): 37-61.

[8]

Massy ZA, Kasiske BL. Post-transplant hyperlipidemia: mechanisms and management. J Am Soc Nephrol. 1996; 7(7): 971-977.

[9]

Tantisattamo E, Molnar MZ, Ho BT, et al. Approach and management of hypertension after kidney transplantation. Front Med (Lausanne). 2020; 7: 229.

[10]

Katabathina VS, Menias CO, Tammisetti VS, et al. Malignancy after solid organ transplantation: comprehensive imaging review. Radiographics. 2016; 36(5): 1390-1407.

[11]

Short S, Lewik G, Issa F. An immune atlas of T cells in transplant rejection: pathways and therapeutic opportunities. Transplantation. 2023; 107(11): 2341-2352.

[12]

Chong AS. Mechanisms of organ transplant injury mediated by B cells and antibodies: implications for antibody-mediated rejection. Am J Transplant. 2020; 20(Suppl 4): 23-32. Suppl 4.

[13]

Elalouf A. Infections after organ transplantation and immune response. Transpl Immunol. 2023; 77: 101798.

[14]

Roberts MB, Fishman JA. Immunosuppressive agents and infectious risk in transplantation: managing the “net state of immunosuppression”. Clin Infect Dis. 2021; 73(7): e1302-e1317.

[15]

Justiz Vaillant AA, Mohseni M. Chronic Transplantation Rejection. StatPearls Publishing; 2024. Copyright ©. 2024. StatPearls Publishing LLC.

[16]

Yang JJ, Baek CH, Kim H, et al. Hyperacute rejection in ABO-incompatible kidney transplantation: significance of isoagglutinin subclass. Transpl Immunol. 2021; 69: 101484.

[17]

Moes DJ, Press RR, Ackaert O, et al. Exploring genetic and non-genetic risk factors for delayed graft function, acute and subclinical rejection in renal transplant recipients. Br J Clin Pharmacol. 2016; 82(1): 227-237.

[18]

Solez K, Colvin RB, Racusen LC, et al. Banff ‘05 Meeting Report: differential diagnosis of chronic allograft injury and elimination of chronic allograft nephropathy (’CAN’). Am J Transplant. 2007; 7(3): 518-526.

[19]

Justiz Vaillant AA, Modi P, Mohammadi O. Graft-Versus-Host Disease. StatPearls Publishing. Copyright © 2024, StatPearls Publishing LLC. 2024.

[20]

Filipovich AH, Weisdorf D, Pavletic S, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: i. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005; 11(12): 945-956.

[21]

Greinix HT, Eikema DJ, Koster L, et al. Improved outcome of patients with graft-versus-host disease after allogeneic hematopoietic cell transplantation for hematologic malignancies over time: an EBMT mega-file study. Haematologica. 2022; 107(5): 1054-1063.

[22]

Zecca M, Prete A, Rondelli R, et al. Chronic graft-versus-host disease in children: incidence, risk factors, and impact on outcome. Blood. 2002; 100(4): 1192-1200.

[23]

Grube M, Holler E, Weber D, Holler B, Herr W, Wolff D. Risk factors and outcome of chronic graft-versus-host disease after allogeneic stem cell transplantation-results from a single-center observational study. Biol Blood Marrow Transplant. 2016; 22(10): 1781-1791.

[24]

Dharnidharka VR, Agodoa LY, Abbott KC. Risk factors for hospitalization for bacterial or viral infection in renal transplant recipients–an analysis of USRDS data. Am J Transplant. 2007; 7(3): 653-661.

[25]

Weinrauch LA, D’Elia JA, Weir MR, et al. Infection and malignancy outweigh cardiovascular mortality in kidney transplant recipients: post hoc analysis of the FAVORIT trial. Am J Med. 2018; 131(2): 165-172.

[26]

Nambiar P, Silibovsky R, Belden KA. Infection in Kidney Transplantation. Contemporary Kidney Transplantation. Springer International Publishing; 2018: 307-327. eds.

[27]

Kritikos A, Manuel O. Bloodstream infections after solid-organ transplantation. Virulence. 2016; 7(3): 329-340.

[28]

Kotton CN. CMV: prevention, diagnosis and therapy. Am J Transplant. 2013; 13(3): 24-40. Suppl. quiz 40.

[29]

Miller S. Monitoring for viral infections in transplant patients. Clin Microbiol Newslett. 2016; 38(16): 129-134.

[30]

Roux A, Canet E, Valade S, et al. Pneumocystis jirovecii pneumonia in patients with or without AIDS, France. Emerg Infect Dis. 2014; 20(9): 1490-1497.

[31]

Pappas PG, Alexander BD, Andes DR, et al. Invasive fungal infections among organ transplant recipients: results of the Transplant-Associated Infection Surveillance Network (TRANSNET). Clin Infect Dis. 2010; 50(8): 1101-1111.

[32]

Fishman JA. Infection in solid-organ transplant recipients. N Engl J Med. 2007; 357(25): 2601-2614.

[33]

Karuthu S, Blumberg EA. Common infections in kidney transplant recipients. Clin J Am Soc Nephrol. 2012; 7(12): 2058-2070.

[34]

Jenssen T, Hartmann A. Post-transplant diabetes mellitus in patients with solid organ transplants. Nat Rev Endocrinol. 2019; 15(3): 172-188.

[35]

Hjelmesaeth J, Hartmann A, Leivestad T, et al. The impact of early-diagnosed new-onset post-transplantation diabetes mellitus on survival and major cardiac events. Kidney Int. 2006; 69(3): 588-595.

[36]

Jørgensen MB, Hornum M, van Hall G, et al. The impact of kidney transplantation on insulin sensitivity. Transpl Int. 2017; 30(3): 295-304.

[37]

Nam JH, Mun JI, Kim SI, et al. beta-Cell dysfunction rather than insulin resistance is the main contributing factor for the development of postrenal transplantation diabetes mellitus. Transplantation. 2001; 71(10): 1417-1423.

[38]

Zelle DM, Corpeleijn E, Deinum J, et al. Pancreatic β-cell dysfunction and risk of new-onset diabetes after kidney transplantation. Diabetes Care. 2013; 36(7): 1926-1932.

[39]

Halden TA, Egeland EJ, Åsberg A, et al. GLP-1 restores altered insulin and glucagon secretion in posttransplantation diabetes. Diabetes Care. 2016; 39(4): 617-624.

[40]

Shah T, Kasravi A, Huang E, et al. Risk factors for development of new-onset diabetes mellitus after kidney transplantation. Transplantation. 2006; 82(12): 1673-1676.

[41]

Kasiske BL, Snyder JJ, Gilbertson D, Matas AJ. Diabetes mellitus after kidney transplantation in the United States. Am J Transplant. 2003; 3(2): 178-185.

[42]

Azadi S, Azarpira N, Roozbeh J, et al. Genetic polymorphisms of glucocorticoid receptor and their association with new-onset diabetes mellitus in kidney transplant recipients. Gene. 2023; 856: 147138.

[43]

Johnston O, Rose CL, Webster AC, Gill JS. Sirolimus is associated with new-onset diabetes in kidney transplant recipients. J Am Soc Nephrol. 2008; 19(7): 1411-1418.

[44]

Gonyea JE, Anderson CF. Weight change and serum lipoproteins in recipients of renal allografts. Mayo Clin Proc. 1992; 67(7): 653-657.

[45]

Becker DM, Markakis M, Sension M, et al. Prevalence of hyperlipidemia in heart transplant recipients. Transplantation. 1987; 44(2): 323-325.

[46]

Dopazo C, Bilbao I, Castells LL, et al. Analysis of adult 20-year survivors after liver transplantation. Hepatol Int. 2015; 9(3): 461-470.

[47]

Warden BA, Duell PB. Management of dyslipidemia in adult solid organ transplant recipients. J Clin Lipidol. 2019; 13(2): 231-245.

[48]

Bucharles SGE, Wallbach KKS, Moraes TP. Pecoits-Filho R. Hypertension in patients on dialysis: diagnosis, mechanisms, and management. J Bras Nefrol. 2019; 41(3): 400-411.

[49]

Przybylowski P, Malyszko J, Malyszko JS, Kobus G, Sadowski J, Mysliwiec M. Blood pressure control in orthotopic heart transplant and kidney allograft recipients is far from satisfactory. Transplant Proc. 2010; 42(10): 4263-4266.

[50]

Savioli G, Surbone S, Giovi I, et al. Early development of metabolic syndrome in patients subjected to lung transplantation. Clin Transplant. 2013; 27(3): E237-243.

[51]

Birdwell KA, Park M. Post-transplant cardiovascular disease. Clin J Am Soc Nephrol. 2021; 16(12): 1878-1889.

[52]

Laskow DA, Curtis JJ. Post-transplant hypertension. Am J Hypertens. 1990; 3(9): 721-725.

[53]

Miller LW. Cardiovascular toxicities of immunosuppressive agents. Am J Transplant. 2002; 2(9): 807-818.

[54]

Poornima I, Power J, Doyle M. Significance of lipid management in cardiac transplant population. J Clin Lipidol. 2019; 13(3): e42-e43.

[55]

Campbell PT, Krim SR. Hypertension in cardiac transplant recipients: tackling a new face of an old foe. Curr Opin Cardiol. 2020; 35(4): 368-375.

[56]

Gillis KA, Patel RK, Jardine AG. Cardiovascular complications after transplantation: treatment options in solid organ recipients. Transplant Rev (Orlando). 2014; 28(2): 47-55.

[57]

Valantine H. Cardiac allograft vasculopathy after heart transplantation: risk factors and management. J Heart Lung Transplant. 2004; 23: S187-193. Suppl.

[58]

Fellström B. Risk factors for and management of post-transplantation cardiovascular disease. BioDrugs. 2001; 15(4): 261-278.

[59]

Krishnan A, Wong G, Teixeira-Pinto A, Lim WH. Incidence and outcomes of early cancers after kidney transplantation. Transpl Int. 2022; 35: 10024.

[60]

Rossi AP, Malignancy KleinCLPosttransplant. Posttransplant Malignancy. Surg Clin North Am. 2019; 99(1): 49-64.

[61]

Collett D, Mumford L, Banner NR, Neuberger J, Watson C. Comparison of the incidence of malignancy in recipients of different types of organ: a UK Registry audit. Am J Transplant. 2010; 10(8): 1889-1896.

[62]

Luskin MR, Heil DS, Tan KS, et al. The impact of EBV status on characteristics and outcomes of posttransplantation lymphoproliferative disorder. Am J Transplant. 2015; 15(10): 2665-2673.

[63]

Verucchi G, Calza L, Trevisani F, et al. Human herpesvirus-8-related Kaposi’s sarcoma after liver transplantation successfully treated with cidofovir and liposomal daunorubicin. Transpl Infect Dis. 2005; 7(1): 34-37.

[64]

Vajdic CM, van Leeuwen MT. Cancer incidence and risk factors after solid organ transplantation. Int J Cancer. 2009; 125(8): 1747-1754.

[65]

Holmes RD, Sokol RJ. Epstein-Barr virus and post-transplant lymphoproliferative disease. Pediatr Transplant. 2002; 6(6): 456-464.

[66]

Al-Mansour Z, Nelson BP, Evens AM. Post-transplant lymphoproliferative disease (PTLD): risk factors, diagnosis, and current treatment strategies. Curr Hematol Malig Rep. 2013; 8(3): 173-183.

[67]

Yao QY, Rowe M, Martin B, Young LS, Rickinson AB. The Epstein-Barr virus carrier state: dominance of a single growth-transforming isolate in the blood and in the oropharynx of healthy virus carriers. J Gen Virol. 1991; 72(Pt 7): 1579-1590.

[68]

Al Hamed R, Bazarbachi AH, Mohty M. Epstein-Barr virus-related post-transplant lymphoproliferative disease (EBV-PTLD) in the setting of allogeneic stem cell transplantation: a comprehensive review from pathogenesis to forthcoming treatment modalities. Bone Marrow Transplant. 2020; 55(1): 25-39.

[69]

Penn I. Cancers complicating organ transplantation. N Engl J Med. 1990; 323(25): 1767-1769.

[70]

Schober T, Framke T, Kreipe H, et al. Characteristics of early and late PTLD development in pediatric solid organ transplant recipients. Transplantation. 2013; 95(1): 240-246.

[71]

Chapman JR, Webster AC, Wong G. Cancer in the transplant recipient. Cold Spring Harb Perspect Med. 2013; 3(7).

[72]

Mannon RB. Delayed graft function: the AKI of kidney transplantation. Nephron. 2018; 140(2): 94-98.

[73]

Siedlecki A, Irish W, Brennan DC. Delayed graft function in the kidney transplant. Am J Transplant. 2011; 11(11): 2279-2296.

[74]

Ponticelli C, Reggiani F, Moroni G. Delayed graft function in kidney transplant: risk factors, consequences and prevention strategies. J Pers Med. 2022; 12(10).

[75]

Ojo AO, Wolfe RA, Held PJ, Port FK, Schmouder RL. Delayed graft function: risk factors and implications for renal allograft survival. Transplantation. 1997; 63(7): 968-974.

[76]

Domański L, Kłoda K, Kwiatkowska E, et al. Effect of delayed graft function, acute rejection and chronic allograft dysfunction on kidney allograft telomere length in patients after transplantation: a prospective cohort study. BMC Nephrol. 2015; 16: 23.

[77]

Cherukuri A, Mehta R, Sood P, Hariharan S. Early allograft inflammation and scarring associate with graft dysfunction and poor outcomes in renal transplant recipients with delayed graft function: a prospective single center cohort study. Transpl Int. 2018; 31(12): 1369-1379.

[78]

Gioco R, Corona D, Ekser B, et al. Gastrointestinal complications after kidney transplantation. World J Gastroenterol. 2020; 26(38): 5797-5811.

[79]

Dahman M, Krell R, Brayman K, et al. Simultaneous Clostridium difficile-associated colitis and late-onset intestinal cytomegalovirus disease in a renal transplant recipient. Ann Transplant. 2010; 15(4): 72-76.

[80]

Rencuzogullari A, Ozuner G, Binboga S, Aytac E, Krishnamurthi V, Gorgun E. Colonic diverticulosis and diverticulitis in renal transplant recipients: management and long-term outcomes. Am Surg. 2017; 83(3): 303-307.

[81]

Lederman ED, Conti DJ, Lempert N, Singh TP, Lee EC. Complicated diverticulitis following renal transplantation. Dis Colon Rectum. 1998; 41(5): 613-618.

[82]

Calogero A, Gallo M, Sica A, et al. Gastroenterological complications in kidney transplant patients. Open Med (Wars). 2020; 15(1): 623-634.

[83]

Dhar R. Neurologic complications of transplantation. Handb Clin Neurol. 2017; 141: 545-572.

[84]

Tardieu L, Divard G, Lortholary O, et al. Cryptococcal meningitis in kidney transplant recipients: a two-decade cohort study in France. Pathogens. 2022; 11(6).

[85]

Tang Q, Dong C, Sun Q. Immune response associated with ischemia and reperfusion injury during organ transplantation. Inflamm Res. 2022; 71(12): 1463-1476.

[86]

Çelik S, Kaynar L, Güven ZT, et al. The effect of danger-associated molecular patterns on survival in acute graft versus host disease. Bone Marrow Transplant. 2024; 59(2): 189-195.

[87]

Hülsdünker J, Ottmüller KJ, Neeff HP, et al. Neutrophils provide cellular communication between ileum and mesenteric lymph nodes at graft-versus-host disease onset. Blood. 2018; 131(16): 1858-1869.

[88]

Fukata M, Vamadevan AS, Abreu MT. Toll-like receptors (TLRs) and Nod-like receptors (NLRs) in inflammatory disorders. Semin Immunol. 2009; 21(4): 242-253.

[89]

Hayden MS, Ghosh S. NF-κB in immunobiology. Cell Res. 2011; 21(2): 223-244.

[90]

Ghosh S, Karin M. Missing pieces in the NF-kappaB puzzle. Cell. 2002; 109: S81-96. Suppl.

[91]

West EE, Kolev M, Kemper C. Complement and the regulation of T cell responses. Annu Rev Immunol. 2018; 36: 309-338.

[92]

Schwab L, Goroncy L, Palaniyandi S, et al. Neutrophil granulocytes recruited upon translocation of intestinal bacteria enhance graft-versus-host disease via tissue damage. Nat Med. 2014; 20(6): 648-654.

[93]

Felix NJ, Donermeyer DL, Horvath S, et al. Alloreactive T cells respond specifically to multiple distinct peptide-MHC complexes. Nat Immunol. 2007; 8(4): 388-397.

[94]

Abou-Daya KI, Oberbarnscheidt MH. Innate allorecognition in transplantation. J Heart Lung Transplant. 2021; 40(7): 557-561.

[95]

DeWolf S, Sykes M. Alloimmune T cells in transplantation. J Clin Invest. 2017; 127(7): 2473-2481.

[96]

Ingulli E. Mechanism of cellular rejection in transplantation. Pediatr Nephrol. 2010; 25(1): 61-74.

[97]

Smyth LA, Lechler RI, Lombardi G. Continuous acquisition of MHC:peptide complexes by recipient cells contributes to the generation of anti-graft CD8(+) T cell immunity. Am J Transplant. 2017; 17(1): 60-68.

[98]

Wood KJ, Zaitsu M, Goto R. Cell mediated rejection. Methods Mol Biol. 2013; 1034: 71-83.

[99]

Toubai T, Mathewson ND, Magenau J, Reddy P. Danger signals and graft-versus-host disease: current understanding and future perspectives. Front Immunol. 2016; 7: 539.

[100]

Gardner D, Jeffery LE, Sansom DM. Understanding the CD28/CTLA-4 (CD152) pathway and its implications for costimulatory blockade. Am J Transplant. 2014; 14(9): 1985-1991.

[101]

Solinas C, Gu-Trantien C, Willard-Gallo K. The rationale behind targeting the ICOS-ICOS ligand costimulatory pathway in cancer immunotherapy. ESMO Open. 2020; 5(1).

[102]

Grewal IS, Flavell RA. The role of CD40 ligand in costimulation and T-cell activation. Immunol Rev. 1996; 153: 85-106.

[103]

Fu Y, Lin Q, Zhang Z, Zhang L. Therapeutic strategies for the costimulatory molecule OX40 in T-cell-mediated immunity. Acta Pharm Sin B. 2020; 10(3): 414-433.

[104]

Wysocki CA, Panoskaltsis-Mortari A, Blazar BR, Serody JS. Leukocyte migration and graft-versus-host disease. Blood. 2005; 105(11): 4191-4199.

[105]

Reina-Campos M, Scharping NE, Goldrath AW. CD8(+) T cell metabolism in infection and cancer. Nat Rev Immunol. 2021; 21(11): 718-738.

[106]

St Paul M, Ohashi PS. The roles of CD8(+) T cell subsets in antitumor immunity. Trends Cell Biol. 2020; 30(9): 695-704.

[107]

Delfs MW, Furukawa Y, Mitchell RN, Lichtman AH. CD8+ T cell subsets TC1 and TC2 cause different histopathologic forms of murine cardiac allograft rejection. Transplantation. 2001; 71(5): 606-610.

[108]

Mittrücker HW, Visekruna A, Huber M. Heterogeneity in the differentiation and function of CD8+ T cells. Arch Immunol Ther Exp (Warsz). 2014; 62(6): 449-458.

[109]

Kemp RA, Ronchese F. Tumor-specific Tc1, but not Tc2, cells deliver protective antitumor immunity. J Immunol. 2001; 167(11): 6497-6502.

[110]

St Paul M, Saibil SD, Lien SC, et al. IL6 induces an IL22(+) CD8(+) T-cell subset with potent antitumor function. Cancer Immunol Res. 2020; 8(3): 321-333.

[111]

Blazar BR, Taylor PA, Vallera DA. CD4+ and CD8+ T cells each can utilize a perforin-dependent pathway to mediate lethal graft-versus-host disease in major histocompatibility complex-disparate recipients. Transplantation. 1997; 64(4): 571-576.

[112]

Zemmour D, Kiner E, Benoist C. CD4(+) teff cell heterogeneity: the perspective from single-cell transcriptomics. Curr Opin Immunol. 2020; 63: 61-67.

[113]

Helper ZhuJT. Cell differentiation, heterogeneity, and plasticity. Cold Spring Harb Perspect Biol. 2018; 10(10).

[114]

Saravia J, Chapman NM, Chi H. Helper T cell differentiation. Cell Mol Immunol. 2019; 16(7): 634-643.

[115]

Zhou L, Chong MM, Littman DR. Plasticity of CD4+ T cell lineage differentiation. Immunity. 2009; 30(5): 646-655.

[116]

Benichou G, Gonzalez B, Marino J, Ayasoufi K, Valujskikh A. Role of memory T cells in allograft rejection and tolerance. Front Immunol. 2017; 8: 170.

[117]

Brehm MA, Daniels KA, Priyadharshini B, et al. Allografts stimulate cross-reactive virus-specific memory CD8 T cells with private specificity. Am J Transplant. 2010; 10(8): 1738-1748.

[118]

Curtsinger JM, Lins DC, Mescher MF. CD8+ memory T cells (CD44high, Ly-6C+) are more sensitive than naive cells to (CD44low, Ly-6C-) to TCR/CD8 signaling in response to antigen. J Immunol. 1998; 160(7): 3236-3243.

[119]

Veiga-Fernandes H, Walter U, Bourgeois C, McLean A, Rocha B. Response of naïve and memory CD8+ T cells to antigen stimulation in vivo. Nat Immunol. 2000; 1(1): 47-53.

[120]

Shiu KY, McLaughlin L, Rebollo-Mesa I, et al. B-lymphocytes support and regulate indirect T-cell alloreactivity in individual patients with chronic antibody-mediated rejection. Kidney Int. 2015; 88(3): 560-568.

[121]

Hong S, Zhang Z, Liu H, et al. B cells are the dominant antigen-presenting cells that activate naive CD4(+) T cells upon immunization with a virus-derived nanoparticle antigen. Immunity. 2018; 49(4): 695-708. e4.

[122]

Noorchashm H, Reed AJ, Rostami SY, et al. B cell-mediated antigen presentation is required for the pathogenesis of acute cardiac allograft rejection. J Immunol. 2006; 177(11): 7715-7722.

[123]

Ng YH, Oberbarnscheidt MH, Chandramoorthy HC, Hoffman R, Chalasani G. B cells help alloreactive T cells differentiate into memory T cells. Am J Transplant. 2010; 10(9): 1970-1980.

[124]

Dalloul A. B-cell-mediated strategies to fight chronic allograft rejection. Front Immunol. 2013; 4: 444.

[125]

Feucht HE, Felber E, Gokel MJ, et al. Vascular deposition of complement-split products in kidney allografts with cell-mediated rejection. Clin Exp Immunol. 1991; 86(3): 464-470.

[126]

Baldwin WM, 3rd, Pruitt SK, Brauer RB, Daha MR, Sanfilippo F. Complement in organ transplantation. Contributions to inflammation, injury, and rejection. Transplantation. 1995; 59(6): 797-808.

[127]

Seidel UJ, Schlegel P, Lang P. Natural killer cell mediated antibody-dependent cellular cytotoxicity in tumor immunotherapy with therapeutic antibodies. Front Immunol. 2013; 4: 76.

[128]

Maeda A, Kogata S, Toyama C, et al. The innate cellular immune response in xenotransplantation. Front Immunol. 2022; 13: 858604.

[129]

Wu GD, Jin YS, Salazar R, et al. Vascular endothelial cell apoptosis induced by anti-donor non-MHC antibodies: a possible injury pathway contributing to chronic allograft rejection. J Heart Lung Transplant. 2002; 21(11): 1174-1187.

[130]

Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science. 2003; 299(5609): 1057-1061.

[131]

Oparaugo NC, Ouyang K, Nguyen NPN, Nelson AM, Agak GW. Human regulatory T cells: understanding the role of Tregs in select autoimmune skin diseases and post-transplant nonmelanoma skin cancers. Int J Mol Sci. 2023; 24(2).

[132]

Asseman C, Mauze S, Leach MW, Coffman RL, Powrie F. An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation. J Exp Med. 1999; 190(7): 995-1004.

[133]

Bejugama K, Taduri G, Guditi S. Effect of regulatory T cells on short-term graft outcome in kidney transplant recipients, a prospective observational, single-center study. Transpl Immunol. 2022; 73: 101630.

[134]

Han JW, Joo DJ, Kim JH, et al. Early reduction of regulatory T cells is associated with acute rejection in liver transplantation under tacrolimus-based immunosuppression with basiliximab induction. Am J Transplant. 2020; 20(8): 2058-2069.

[135]

Rieger K, Loddenkemper C, Maul J, et al. Mucosal FOXP3+ regulatory T cells are numerically deficient in acute and chronic GvHD. Blood. 2006; 107(4): 1717-1723.

[136]

Fondi C, Nozzoli C, Benemei S, et al. Increase in FOXP3+ regulatory T cells in GVHD skin biopsies is associated with lower disease severity and treatment response. Biol Blood Marrow Transplant. 2009; 15(8): 938-947.

[137]

Hoffmann P, Ermann J, Edinger M, Fathman CG, Strober S. Donor-type CD4(+)CD25(+) regulatory T cells suppress lethal acute graft-versus-host disease after allogeneic bone marrow transplantation. J Exp Med. 2002; 196(3): 389-399.

[138]

Taylor PA, Lees CJ, Blazar BR. The infusion of ex vivo activated and expanded CD4(+)CD25(+) immune regulatory cells inhibits graft-versus-host disease lethality. Blood. 2002; 99(10): 3493-3499.

[139]

Di Ianni M, Falzetti F, Carotti A, et al. Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation. Blood. 2011; 117(14): 3921-3928.

[140]

Jin N, Malcherek G, Mani J, et al. Suppression of cytomegalovirus-specific CD8(+)T cells by everolimus. Leuk Lymphoma. 2014; 55(5): 1144-1150.

[141]

Nakayama K, Nakauchi H. Cyclosporin A inhibits the decrease of CD4/CD8 expression induced by protein kinase C activation. Int Immunol. 1993; 5(4): 419-426.

[142]

Shi X, Zhang M, Liu F, et al. Tim-1-Fc suppresses chronic cardiac allograft rejection and vasculopathy by reducing IL-17 production. Int J Clin Exp Pathol. 2014; 7(2): 509-520.

[143]

Holcombe H, Mellman I, Janeway CA, Jr., Bottomly K, Dittel BN. The immunosuppressive agent 15-deoxyspergualin functions by inhibiting cell cycle progression and cytokine production following naive T cell activation. J Immunol. 2002; 169(9): 4982-4989.

[144]

Havele C, Paetkau V. Cyclosporine blocks the activation of antigen-dependent cytotoxic T lymphocytes directly by an IL-2-independent mechanism. J Immunol. 1988; 140(10): 3303-3308.

[145]

Zhan X, Brown B, Slobod KS, Hurwitz JL. Inhibition of ex vivo-expanded cytotoxic T-lymphocyte function by high-dose cyclosporine. Transplantation. 2003; 76(4): 739-740.

[146]

Blaheta RA, Leckel K, Wittig B, et al. Inhibition of endothelial receptor expression and of T-cell ligand activity by mycophenolate mofetil. Transpl Immunol. 1998; 6(4): 251-259.

[147]

Lv QK, Liu JX, Li SN, et al. Mycophenolate mofetil modulates differentiation of Th1/Th2 and the secretion of cytokines in an active Crohn’s disease mouse model. Int J Mol Sci. 2015; 16(11): 26654-26666.

[148]

Wang GN, Xiong Y, Ye J, Zhang LH, Ye XS. Synthetic N-alkylated iminosugars as new potential immunosuppressive agents. ACS Med Chem Lett. 2011; 2(9): 682-686.

[149]

Xiang M, Liu T, Tan W, et al. Effects of kinsenoside, a potential immunosuppressive drug for autoimmune hepatitis, on dendritic cells/CD8(+) T cells communication in mice. Hepatology. 2016; 64(6): 2135-2150.

[150]

Tomita Y, Uehara S, Takiguchi S, Nakamura M. Effect of mammalian target of rapamycin inhibition on activated regulatory T-cell expansion in kidney transplantation. Transplant Proc. 2023; 55(4): 792-796.

[151]

Janyst M, Kaleta B, Janyst K, Zagożdżon R, Kozlowska E, Lasek W. Comparative study of immunomodulatory agents to induce human T regulatory (Treg) cells: preferential Treg-stimulatory effect of prednisolone and rapamycin. Arch Immunol Ther Exp (Warsz). 2020; 68(4): 20.

[152]

Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol. 2003; 4(4): 330-336.

[153]

Qu Y, Zhang B, Zhao L, et al. The effect of immunosuppressive drug rapamycin on regulatory CD4+CD25+Foxp3+T cells in mice. Transpl Immunol. 2007; 17(3): 153-161.

[154]

Battaglia M, Stabilini A, Roncarolo MG. Rapamycin selectively expands CD4+CD25+FoxP3+ regulatory T cells. Blood. 2005; 105(12): 4743-4748.

[155]

Anderson AC, Joller N, Kuchroo VK. Lag-3, Tim-3, and TIGIT: co-inhibitory receptors with specialized functions in immune regulation. Immunity. 2016; 44(5): 989-1004.

[156]

Stecher C, Battin C, Leitner J, et al. PD-1 blockade promotes emerging checkpoint inhibitors in enhancing T cell responses to allogeneic dendritic cells. Front Immunol. 2017; 8: 572.

[157]

Zeng Q, Yuan X, Cao J, et al. Mycophenolate mofetil enhances the effects of tacrolimus on the inhibitory function of regulatory T cells in patients after liver transplantation via PD-1 and TIGIT receptors. Immunopharmacol Immunotoxicol. 2021; 43(2): 239-246.

[158]

Chen X, Li S, Long D, Shan J, Li Y. Rapamycin facilitates differentiation of regulatory T cells via enhancement of oxidative phosphorylation. Cell Immunol. 2021; 365: 104378.

[159]

Setoguchi R, Hori S, Takahashi T, Sakaguchi S. Homeostatic maintenance of natural Foxp3(+) CD25(+) CD4(+) regulatory T cells by interleukin (IL)-2 and induction of autoimmune disease by IL-2 neutralization. J Exp Med. 2005; 201(5): 723-735.

[160]

Cao X, Cai SF, Fehniger TA, et al. Granzyme B and perforin are important for regulatory T cell-mediated suppression of tumor clearance. Immunity. 2007; 27(4): 635-646.

[161]

Uyttenhove C, Pilotte L, Théate I, et al. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2, 3-dioxygenase. Nat Med. 2003; 9(10): 1269-1274.

[162]

Moosmann A, Bigalke I, Tischer J, et al. Effective and long-term control of EBV PTLD after transfer of peptide-selected T cells. Blood. 2010; 115(14): 2960-2970.

[163]

Volk V, Theobald SJ, Danisch S, et al. PD-1 blockade aggravates Epstein-Barr virus(+) post-transplant lymphoproliferative disorder in humanized mice resulting in central nervous system involvement and CD4(+) T cell dysregulations. Front Oncol. 2020; 10: 614876.

[164]

Brink AA, ten Berge RL, van den Brule AJ, Willemze R, Chott A, Meijer CJ. Epstein-Barr virus is present in neoplastic cytotoxic T cells in extranodal, and predominantly in B cells in nodal T non-Hodgkin lymphomas. J Pathol. 2000; 191(4): 400-406.

[165]

Tanaka T, Takizawa J, Miyakoshi S, et al. Manifestations of fulminant CD8 T-cell post-transplant lymphoproliferative disorder following the administration of rituximab for lymphadenopathy with a high level of Epstein-Barr Virus (EBV) replication after allogeneic hematopoietic stem cell transplantation. Intern Med. 2014; 53(18): 2115-2119.

[166]

Jagadeesh D, Woda BA, Draper J, Evens AM. Post transplant lymphoproliferative disorders: risk, classification, and therapeutic recommendations. Curr Treat Options Oncol. 2012; 13(1): 122-136.

[167]

Macedo C, Donnenberg A, Popescu I, et al. EBV-specific memory CD8+ T cell phenotype and function in stable solid organ transplant patients. Transpl Immunol. 2005; 14(2): 109-116.

[168]

Yousif E, Abdelwahab A. Post-transplant diabetes mellitus in kidney transplant recipients in sudan: a comparison between tacrolimus and cyclosporine-based immunosuppression. Cureus. 2022; 14(2): e22285.

[169]

Sato T, Inagaki A, Uchida K, et al. Diabetes mellitus after transplant: relationship to pretransplant glucose metabolism and tacrolimus or cyclosporine A-based therapy. Transplantation. 2003; 76(9): 1320-1326.

[170]

Araki M, Flechner SM, Ismail HR, et al. Posttransplant diabetes mellitus in kidney transplant recipients receiving calcineurin or mTOR inhibitor drugs. Transplantation. 2006; 81(3): 335-341.

[171]

Lebranchu Y, Snanoudj R, Toupance O, et al. Five-year results of a randomized trial comparing de novo sirolimus and cyclosporine in renal transplantation: the SPIESSER study. Am J Transplant. 2012; 12(7): 1801-1810.

[172]

Duijnhoven EMV, Boots JMM, Christiaans MHL, Wolffenbuttel BHR, Hooff JPV. Influence of tacrolimus on glucose metabolism before and after renal transplantation: a prospective study. J Am Soc Nephrol. 2001; 12(3): 583-588.

[173]

Boots JMM, van Duijnhoven EM, Christiaans MHL, Wolffenbuttel BHR, van Hooff JP. Glucose metabolism in renal transplant recipients on tacrolimus: the effect of steroid withdrawal and tacrolimus trough level reduction. J Am Soc Nephrol. 2002; 13(1): 221-227.

[174]

Shivaswamy V, Bennett RG, Clure CC, et al. Tacrolimus and sirolimus have distinct effects on insulin signaling in male and female rats. Transl Res. 2014; 163(3): 221-231.

[175]

Larsen JL, Bennett RG, Burkman T, et al. Tacrolimus and sirolimus cause insulin resistance in normal sprague dawley rats. Transplantation. 2006; 82(4): 466-470.

[176]

Pagano G, Bruno A, Cavallo-Perin P, Cesco L, Imbimbo B. Glucose intolerance after short-term administration of corticosteroids in healthy subjects. Prednisone, deflazacort, and betamethasone. Arch Intern Med. 1989; 149(5): 1098-1101.

[177]

Kobashigawa JA, Kasiske BL. Hyperlipidemia in solid organ transplantation. Transplantation. 1997; 63(3): 331-338.

[178]

Agarwal A, Prasad GV. Post-transplant dyslipidemia: mechanisms, diagnosis and management. World J Transplant. 2016; 6(1): 125-134.

[179]

de Groen PC. Cyclosporine, low-density lipoprotein, and cholesterol. Mayo Clin Proc. 1988; 63(10): 1012-1021.

[180]

Bloom IT, Bentley FR, Garrison RN. Acute cyclosporine-induced renal vasoconstriction is mediated by endothelin-1. Surgery. 1993; 114(2). 480-487. discussion 487–8.

[181]

Taler SJ, Textor SC, Canzanello VJ, Schwartz L. Cyclosporin-induced hypertension: incidence, pathogenesis and management. Drug Saf. 1999; 20(5): 437-449.

[182]

Thomas B, Weir MR. The evaluation and therapeutic management of hypertension in the transplant patient. Curr Cardiol Rep. 2015; 17(11): 95.

[183]

Curtis JJ, Luke RG, Jones P, Diethelm AG. Hypertension in cyclosporine-treated renal transplant recipients is sodium dependent. Am J Med. 1988; 85(2): 134-138.

[184]

Moss NG, Powell SL, Falk RJ. Intravenous cyclosporine activates afferent and efferent renal nerves and causes sodium retention in innervated kidneys in rats. Proc Natl Acad Sci USA. 1985; 82(23): 8222-8226.

[185]

Lakkis JI, Weir MR. Treatment-resistant hypertension in the transplant recipient. Semin Nephrol. 2014; 34(5): 560-570.

[186]

Bahous SA, Stephan A, Blacher J, Safar ME. Aortic stiffness, living donors, and renal transplantation. Hypertension. 2006; 47(2): 216-221.

[187]

Lin Y, Wang L, Ge W, et al. Multi-omics network characterization reveals novel microRNA biomarkers and mechanisms for diagnosis and subtyping of kidney transplant rejection. J Transl Med. 2021; 19(1): 346.

[188]

Cheng CY, Feng YT, Wang HY. Incidence and relative risk factors in posttransplant diabetes mellitus patients: a retrospective cohort study. Korean J Transplant. 2020; 34(4): 213-237.

[189]

Driscoll CJ, Cashion AK, Hathaway DK, et al. Posttransplant diabetes mellitus in liver transplant recipients. Prog Transplant. 2006; 16(2): 110-116.

[190]

Mohammad KG, Idrees MK, Ali T, Akhtar F. Posttransplant diabetes mellitus among live-related kidney transplant recipients: Sindh Institute of Urology and Transplantation experience. Saudi J Kidney Dis Transpl. 2018; 29(6): 1320-1325.

[191]

Mazali FC, Lalli CA, Alves-Filho G, Mazzali M. Posttransplant diabetes mellitus: incidence and risk factors. Transplant Proc. 2008; 40(3): 764-766.

[192]

Roccaro GA, Mitrani R, Hwang WT, Forde KA, Reddy KR. Sustained virological response is associated with a decreased risk of posttransplant diabetes mellitus in liver transplant recipients with hepatitis C-related liver disease. Liver Transpl. 2018; 24(12): 1665-1672.

[193]

Hjelmesaeth J, Müller F, Jenssen T, Rollag H, Sagedal S, Hartmann A. Is there a link between cytomegalovirus infection and new-onset posttransplantation diabetes mellitus? Potential mechanisms of virus induced beta-cell damage. Nephrol Dial Transplant. 2005; 20(11): 2311-2315.

[194]

Masini M, Campani D, Boggi U, et al. Hepatitis C virus infection and human pancreatic beta-cell dysfunction. Diabetes Care. 2005; 28(4): 940-941.

[195]

Wang Q, Chen J, Wang Y, Han X, Chen X. Hepatitis C virus induced a novel apoptosis-like death of pancreatic beta cells through a caspase 3-dependent pathway. PLoS One. 2012; 7(6): e38522.

[196]

Chen J, Wang F, Zhou Y, et al. Chronic hepatitis C virus infection impairs insulin secretion by regulation of p38δ MAPK-dependent exocytosis in pancreatic β-cells. Clin Sci (Lond). 2020; 134(5): 529-542.

[197]

Kawaguchi T, Yoshida T, Harada M, et al. Hepatitis C virus down-regulates insulin receptor substrates 1 and 2 through up-regulation of suppressor of cytokine signaling 3. Am J Pathol. 2004; 165(5): 1499-1508.

[198]

Domma AJ, Henderson LA, Goodrum FD, Moorman NJ, Kamil JP. Human cytomegalovirus attenuates AKT activity by destabilizing insulin receptor substrate proteins. J Virol. 2023; 97(10): e0056323.

[199]

Banerjee S, Saito K, Ait-Goughoulte M, Meyer K, Ray RB, Ray R. Hepatitis C virus core protein upregulates serine phosphorylation of insulin receptor substrate-1 and impairs the downstream akt/protein kinase B signaling pathway for insulin resistance. J Virol. 2008; 82(6): 2606-2612.

[200]

Bose SK, Shrivastava S, Meyer K, Ray RB, Ray R. Hepatitis C virus activates the mTOR/S6K1 signaling pathway in inhibiting IRS-1 function for insulin resistance. J Virol. 2012; 86(11): 6315-6322.

[201]

Jia B, Wang Y, Yu G, et al. Naringenin ameliorates insulin resistance by modulating endoplasmic reticulum stress in hepatitis C virus-infected liver. Biomed Pharmacother. 2019; 115: 108848.

[202]

Perlemuter G, Sabile A, Letteron P, et al. Hepatitis C virus core protein inhibits microsomal triglyceride transfer protein activity and very low density lipoprotein secretion: a model of viral-related steatosis. Faseb J. 2002; 16(2): 185-194.

[203]

Hui J, Qu YY, Tang N, et al. Association of cytomegalovirus infection with hypertension risk: a meta-analysis. Wien Klin Wochenschr. 2016; 128(15-16): 586-591.

[204]

Cheng J, Ke Q, Jin Z, et al. Cytomegalovirus infection causes an increase of arterial blood pressure. PLoS Pathog. 2009; 5(5): e1000427.

[205]

Grahame-Clarke C, Chan NN, Andrew D, et al. Human cytomegalovirus seropositivity is associated with impaired vascular function. Circulation. 2003; 108(6): 678-683.

[206]

Bentz GL, Yurochko AD. Human CMV infection of endothelial cells induces an angiogenic response through viral binding to EGF receptor and beta1 and beta3 integrins. Proc Natl Acad Sci USA. 2008; 105(14): 5531-5536.

[207]

Rahbar A, Söderberg-Nauclér C. Human cytomegalovirus infection of endothelial cells triggers platelet adhesion and aggregation. J Virol. 2005; 79(4): 2211-2220.

[208]

Gredmark-Russ S, Dzabic M, Rahbar A, et al. Active cytomegalovirus infection in aortic smooth muscle cells from patients with abdominal aortic aneurysm. J Mol Med (Berl). 2009; 87(4): 347-356.

[209]

Maggi P, Calò F, Messina V, et al. Cardiovascular disease risk in liver transplant recipients transplanted due to chronic viral hepatitis. PLoS One. 2022; 17(3): e0265178.

[210]

Chew KW, Hua L, Bhattacharya D, et al. The effect of hepatitis C virologic clearance on cardiovascular disease biomarkers in human immunodeficiency virus/hepatitis C virus coinfection. Open Forum Infect Dis. 2014; 1(3): ofu104.

[211]

Castellon X, Bogdanova V. Chronic inflammatory diseases and endothelial dysfunction. Aging Dis. 2016; 7(1): 81-89.

[212]

Boddi M, Abbate R, Chellini B, et al. Hepatitis C virus RNA localization in human carotid plaques. J Clin Virol. 2010; 47(1): 72-75.

[213]

Fletcher NF, Wilson GK, Murray J, et al. Hepatitis C virus infects the endothelial cells of the blood-brain barrier. Gastroenterology. 2012; 142(3): 634-643.

[214]

Massy ZA. Hyperlipidemia and cardiovascular disease after organ transplantation. Transplantation. 2001; 72: S13-15. Suppl.

[215]

Wang H, Peng G, Bai J, et al. Cytomegalovirus infection and relative risk of cardiovascular disease (ischemic heart disease, stroke, and cardiovascular death): a meta-analysis of prospective studies up to 2016. J Am Heart Assoc. 2017; 6(7).

[216]

Yates TA, Griffith GJ, Morris TT. Human cytomegalovirus and risk of incident cardiovascular disease in UK Biobank. J Infect Dis. 2022; 225(7): 1301-1302.

[217]

Rodríguez-Goncer I, Fernández-Ruiz M, Aguado JM. A critical review of the relationship between post-transplant atherosclerotic events and cytomegalovirus exposure in kidney transplant recipients. Expert Rev Anti Infect Ther. 2020; 18(2): 113-125.

[218]

Eerdmans PH, Persoons MC, Debets SJ, et al. Impaired arterial reactivity following cytomegalovirus infection in the immunosuppressed rat. Br J Pharmacol. 1996; 119(4): 637-646.

[219]

Aguilera V, Di Maira T, Conde I, et al. Cytomegalovirus reactivation in liver transplant recipients due to hepatitis C cirrhosis is associated with higher cardiovascular risk—an observational, retrospective study. Transpl Int. 2018; 31(6): 649-657.

[220]

Halloran PF. Immunosuppressive drugs for kidney transplantation. N Engl J Med. 2004; 351(26): 2715-2729.

[221]

Tönshoff B. Immunosuppressants in organ transplantation. Handb Exp Pharmacol. 2020; 261: 441-469.

[222]

Parlakpinar H, Gunata M. Transplantation and immunosuppression: a review of novel transplant-related immunosuppressant drugs. Immunopharmacol Immunotoxicol. 2021; 43(6): 651-665.

[223]

Szumilas K, Wilk A, Wiśniewski P, et al. Current status regarding immunosuppressive treatment in patients after renal transplantation. Int J Mol Sci. 2023; 24(12).

[224]

Bauer AC, Franco RF, Manfro RC. Immunosuppression in kidney transplantation: state of the art and current protocols. Curr Pharm Des. 2020; 26(28): 3440-3450.

[225]

Wagner SJ, Brennan DC. Induction therapy in renal transplant recipients. Drugs. 2012; 72: 671-683.

[226]

Wu Q, Wang X, Nepovimova E, Wang Y, Yang H, Kuca K. Mechanism of cyclosporine A nephrotoxicity: oxidative stress, autophagy, and signalings. Food Chem Toxicol. 2018; 118: 889-907.

[227]

Kajiwara M, Masuda S. Role of mTOR inhibitors in kidney disease. Int J Mol Sci. 2016; 17(6).

[228]

Saran U, Foti M, Dufour JF. Cellular and molecular effects of the mTOR inhibitor everolimus. Clin Sci (Lond). 2015; 129(10): 895-914.

[229]

Ayroldi E, Cannarile L, Migliorati G, Nocentini G, Delfino DV, Riccardi C. Mechanisms of the anti-inflammatory effects of glucocorticoids: genomic and nongenomic interference with MAPK signaling pathways. Faseb J. 2012; 26(12): 4805-4820.

[230]

Chandran S, Tang Q, Sarwal M, et al. Polyclonal regulatory T cell therapy for control of inflammation in kidney transplants. Am J Transplant. 2017; 17(11): 2945-2954.

[231]

Mathew JM, HV J, LeFever A, et al. A phase I clinical trial with ex vivo expanded recipient regulatory T cells in living donor kidney transplants. Sci Rep. 2018; 8(1): 7428.

[232]

Sawitzki B, Harden PN, Reinke P, et al. Regulatory cell therapy in kidney transplantation (The ONE Study): a harmonised design and analysis of seven non-randomised, single-arm, phase 1/2A trials. Lancet. 2020; 395(10237): 1627-1639.

[233]

Sánchez-Fueyo A, Whitehouse G, Grageda N, et al. Applicability, safety, and biological activity of regulatory T cell therapy in liver transplantation. Am J Transplant. 2020; 20(4): 1125-1136.

[234]

Todo S, Yamashita K, Goto R, et al. A pilot study of operational tolerance with a regulatory T-cell-based cell therapy in living donor liver transplantation. Hepatology. 2016; 64(2): 632-643.

[235]

Kasiske BL, Cangro CB, Hariharan S, et al. The evaluation of renal transplantation candidates: clinical practice guidelines. Am J Transplant. 2001; 1(2): 3-95. Suppl.

[236]

Danzinger-Isakov L, Kumar D. Guidelines for vaccination of solid organ transplant candidates and recipients. Am J Transplant. 2009: S258-262. Suppl.

[237]

Kliem V, Fricke L, Wollbrink T, Burg M, Radermacher J, Rohde F. Improvement in long-term renal graft survival due to CMV prophylaxis with oral ganciclovir: results of a randomized clinical trial. Am J Transplant. 2008; 8(5): 975-983.

[238]

Jha V. Post-transplant infections: an ounce of prevention. Indian J Nephrol. 2010; 20(4): 171-178.

[239]

Schaffner A. Pretransplant evaluation for infections in donors and recipients of solid organs. Clin Infect Dis. 2001; 33(1): S9-14. Suppl.

[240]

Asberg A, Humar A, Jardine AG, et al. Long-term outcomes of CMV disease treatment with valganciclovir versus IV ganciclovir in solid organ transplant recipients. Am J Transplant. 2009; 9(5): 1205-1213.

[241]

Allen U, Preiksaitis J. Epstein-barr virus and posttransplant lymphoproliferative disorder in solid organ transplant recipients. Am J Transplant. 2009; 9(4): S87-96. Suppl.

[242]

KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant. 2009; 9 Suppl (3): S1-155.

[243]

Subramanian A, Dorman S. Mycobacterium tuberculosis in solid organ transplant recipients. Am J Transplant. 2009; 9(4): S57-62. Suppl.

[244]

Kwon S, Kim YC, Kwon H, et al. Metformin use and long-term clinical outcomes in kidney transplant recipients. Am J Kidney Dis. 2023; 82(3): 290-299. e1.

[245]

Haidinger M, Antlanger M, Kopecky C, Kovarik JJ, Säemann MD, Werzowa J. Post-transplantation diabetes mellitus: evaluation of treatment strategies. Clin Transplant. 2015; 29(5): 415-424.

[246]

Türk T, Pietruck F, Dolff S, et al. Repaglinide in the management of new-onset diabetes mellitus after renal transplantation. Am J Transplant. 2006; 6(4): 842-846.

[247]

Sharif A. Should metformin be our antiglycemic agent of choice post-transplantation? Am J Transplant. 2011; 11(7): 1376-1381.

[248]

Shivaswamy V, Bennett RG, Clure CC, Larsen JL, Hamel FG. Metformin improves immunosuppressant induced hyperglycemia and exocrine apoptosis in rats. Transplantation. 2013; 95(2): 280-284.

[249]

Kurian B, Joshi R, Helmuth A. Effectiveness and long-term safety of thiazolidinediones and metformin in renal transplant recipients. Endocr Pract. 2008; 14(8): 979-984.

[250]

Stephen J, Anderson-Haag TL, Gustafson S, Snyder JJ, Kasiske BL, Israni AK. Metformin use in kidney transplant recipients in the United States: an observational study. Am J Nephrol. 2014; 40(6): 546-553.

[251]

2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Atherosclerosis. 2019; 290: 140-205.

[252]

Blum A, Shamburek R. The pleiotropic effects of statins on endothelial function, vascular inflammation, immunomodulation and thrombogenesis. Atherosclerosis. 2009; 203(2): 325-330.

[253]

Riella LV, Gabardi S, Chandraker A. Dyslipidemia and its therapeutic challenges in renal transplantation. Am J Transplant. 2012; 12(8): 1975-1982.

[254]

Terker AS, Yang CL, McCormick JA, et al. Sympathetic stimulation of thiazide-sensitive sodium chloride cotransport in the generation of salt-sensitive hypertension. Hypertension. 2014; 64(1): 178-184.

[255]

Taber DJ, Srinivas TM, Pilch NA, et al. Are thiazide diuretics safe and effective antihypertensive therapy in kidney transplant recipients? Am J Nephrol. 2013; 38(4): 285-291.

[256]

Anis KH, Weinrauch LA, D’Elia JA. Effects of smoking on solid organ transplantation outcomes. Am J Med. 2019; 132(4): 413-419.

[257]

Tuomilehto J, Lindström J, Eriksson JG, et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001; 344(18): 1343-1350.

[258]

Wissing KM, Abramowicz D, Weekers L, et al. Prospective randomized study of conversion from tacrolimus to cyclosporine A to improve glucose metabolism in patients with posttransplant diabetes mellitus after renal transplantation. Am J Transplant. 2018; 18(7): 1726-1734.

[259]

Kim HD, Chang JY, Chung BH, et al. Effect of everolimus with low-dose tacrolimus on development of new-onset diabetes after transplantation and allograft function in kidney transplantation: a multicenter, open-label. Ann Transplant. 2021; 26: e927984. Randomized Trial.

[260]

Wen X, Casey MJ, Santos AH, Hartzema A, Womer KL. Comparison of utilization and clinical outcomes for belatacept-and tacrolimus-based immunosuppression in renal transplant recipients. Am J Transplant. 2016; 16(11): 3202-3211.

[261]

White M, Haddad H, Leblanc MH, et al. Conversion from cyclosporine microemulsion to tacrolimus-based immunoprophylaxis improves cholesterol profile in heart transplant recipients with treated but persistent dyslipidemia: the Canadian multicentre randomized trial of tacrolimus vs cyclosporine microemulsion. J Heart Lung Transplant. 2005; 24(7): 798-809.

[262]

Vincenti F, Charpentier B, Vanrenterghem Y, et al. A phase III study of belatacept-based immunosuppression regimens versus cyclosporine in renal transplant recipients (BENEFIT study). Am J Transplant. 2010; 10(3): 535-546.

[263]

Vanrenterghem Y, Bresnahan B, Campistol J, et al. Belatacept-based regimens are associated with improved cardiovascular and metabolic risk factors compared with cyclosporine in kidney transplant recipients (BENEFIT and BENEFIT-EXT studies). Transplantation. 2011; 91(9): 976-983.

[264]

Jardine AG, Fellström B, Logan JO, et al. Cardiovascular risk and renal transplantation: post hoc analyses of the assessment of lescol in renal transplantation (ALERT) Study. Am J Kidney Dis. 2005; 46(3): 529-536.

[265]

Soveri I, Holdaas H, Jardine A, Gimpelewicz C, Staffler B, Fellström B. Renal transplant dysfunction–importance quantified in comparison with traditional risk factors for cardiovascular disease and mortality. Nephrol Dial Transplant. 2006; 21(8): 2282-2289.

[266]

Vincenti F, Blancho G, Durrbach A, et al. Five-year safety and efficacy of belatacept in renal transplantation. J Am Soc Nephrol. 2010; 21(9): 1587-1596.

[267]

Pontrelli P, Rascio F, Zaza G, et al. Interleukin-27 is a potential marker for the onset of post-transplant malignancies. Nephrol Dial Transplant. 2019; 34(1): 157-166.

[268]

Zhang S, Fujita H, Mitsui H, et al. Increased Tc22 and Treg/CD8 ratio contribute to aggressive growth of transplant associated squamous cell carcinoma. PLoS One. 2013; 8(5): e62154.

[269]

Coles SJ, Hills RK, Wang EC, et al. Increased CD200 expression in acute myeloid leukemia is linked with an increased frequency of FoxP3+ regulatory T cells. Leukemia. 2012; 26(9): 2146-2148.

[270]

Olteanu H, Harrington AM, Hari P, Kroft SH. CD200 expression in plasma cell myeloma. Br J Haematol. 2011; 153(3): 408-411.

[271]

Gorczynski RM. CD200 and its receptors as targets for immunoregulation. Curr Opin Investig Drugs. 2005; 6(5): 483-488.

[272]

Vaughan JW, Shi M, Horna P, Olteanu H. Increased CD200 expression in post-transplant lymphoproliferative disorders correlates with an increased frequency of FoxP3(+) regulatory T cells. Ann Diagn Pathol. 2020; 48: 151585.

[273]

Van den Hove LE, Vandenberghe P, Van Gool SW, et al. Peripheral blood lymphocyte subset shifts in patients with untreated hematological tumors: evidence for systemic activation of the T cell compartment. Leuk Res. 1998; 22(2): 175-184.

[274]

Tsukishiro T, Donnenberg AD, Whiteside TL. Rapid turnover of the CD8(+)CD28(-) T-cell subset of effector cells in the circulation of patients with head and neck cancer. Cancer Immunol Immunother. 2003; 52(10): 599-607.

[275]

Bottomley MJ, Harden PN, Wood KJ. CD8+ immunosenescence predicts post-transplant cutaneous squamous cell carcinoma in high-risk patients. J Am Soc Nephrol. 2016; 27(5): 1505-1515.

[276]

Courivaud C, Bamoulid J, Gaugler B, et al. Cytomegalovirus exposure, immune exhaustion and cancer occurrence in renal transplant recipients. Transpl Int. 2012; 25(9): 948-955.

[277]

Lau E, Moyers JT, Wang BC, et al. Analysis of post-transplant lymphoproliferative disorder (PTLD) outcomes with Epstein-Barr Virus (EBV) assessments—a single tertiary referral center experience and review of literature. Cancers (Basel). 2021; 13(4).

[278]

Rosselet A, Vu DH, Meylan P, et al. Associations of serum EBV DNA and gammopathy with post-transplant lymphoproliferative disease. Clin Transplant. 2009; 23(1): 74-82.

[279]

Suresh S, Dix D, Wang L, Blydt-Hansen TD. High urinary CXCL10/Cr with onset of Burkitt lymphoma in a pediatric kidney transplant recipient. Pediatr Transplant. 2022; 26(7): e14354.

[280]

Mukherjee S, Mukherjee U. A comprehensive review of immunosuppression used for liver transplantation. J Transplant. 2009; 2009: 701464.

[281]

Diekmann F, Andrés A. Oppenheimer F. mTOR inhibitor-associated proteinuria in kidney transplant recipients. Transplant Rev (Orlando). 2012; 26(1): 27-29.

[282]

Campbell SB, Walker R, Tai SS, Jiang Q, Russ GR. Randomized controlled trial of sirolimus for renal transplant recipients at high risk for nonmelanoma skin cancer. Am J Transplant. 2012; 12(5): 1146-1156.

[283]

Knoll GA, Kokolo MB, Mallick R, et al. Effect of sirolimus on malignancy and survival after kidney transplantation: systematic review and meta-analysis of individual patient data. Bmj. 2014; 349: g6679.

[284]

Yanik EL, Siddiqui K, Engels EA. Sirolimus effects on cancer incidence after kidney transplantation: a meta-analysis. Cancer Med. 2015; 4(9): 1448-1459.

[285]

Engelman JA. Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat Rev Cancer. 2009; 9(8): 550-562.

[286]

Dees S, Ganesan R, Singh S, Grewal IS. Regulatory T cell targeting in cancer: emerging strategies in immunotherapy. Eur J Immunol. 2021; 51(2): 280-291.

[287]

Rosskopf S, Leitner J, Zlabinger GJ, Steinberger P. CTLA-4 antibody ipilimumab negatively affects CD4(+) T-cell responses in vitro. Cancer Immunol Immunother. 2019; 68(8): 1359-1368.

[288]

Derman BA, Zha Y, Zimmerman TM, et al. Regulatory T-cell depletion in the setting of autologous stem cell transplantation for multiple myeloma: pilot study. J Immunother Cancer. 2020; 8(1).

[289]

Thibodeaux SR, Barnett BB, Pandeswara S, et al. IFNα augments clinical efficacy of regulatory T-cell depletion with denileukin diftitox in ovarian cancer. Clin Cancer Res. 2021; 27(13): 3661-3673.

[290]

Campbell JR, McDonald BR, Mesko PB, et al. Fc-optimized anti-CCR8 antibody depletes regulatory T cells in human tumor models. Cancer Res. 2021; 81(11): 2983-2994.

[291]

Dao T, Mun SS, Scott AC, et al. Depleting T regulatory cells by targeting intracellular Foxp3 with a TCR mimic antibody. Oncoimmunology. 2019; 8(7): 1570778.

[292]

Oweida AJ, Darragh L, Phan A, et al. STAT3 modulation of regulatory T cells in response to radiation therapy in head and neck cancer. J Natl Cancer Inst. 2019; 111(12): 1339-1349.

[293]

Son CH, Bae JH, Shin DY, et al. Combination effect of regulatory T-cell depletion and ionizing radiation in mouse models of lung and colon cancer. Int J Radiat Oncol Biol Phys. 2015; 92(2): 390-398.

[294]

Moatti A, Debesset A, Pilon C, et al. TNFR2 blockade of regulatory T cells unleashes an antitumor immune response after hematopoietic stem-cell transplantation. J Immunother Cancer. 2022; 10(4).

[295]

Davids MS, Kim HT, Bachireddy P, et al. Ipilimumab for patients with relapse after allogeneic transplantation. N Engl J Med. 2016; 375(2): 143-153.

[296]

Dang BN, Ch’ng J, Russell M, Cheng JC, Moore TB, Alejos JC. Treatment of post-transplant lymphoproliferative disorder (PTLD) in a heart transplant recipient with chimeric antigen receptor T-cell therapy. Pediatr Transplant. 2021; 25(5): e13861.

[297]

Oren D, DeFilippis EM, Lotan D, et al. Successful CAR T cell therapy in a heart and kidney transplant recipient with refractory PTLD. JACC CardioOncol. 2022; 4(5): 713-716.

[298]

Hernani R, Sancho A, Amat P, et al. CAR-T therapy in solid transplant recipients with post-transplant lymphoproliferative disease: case report and literature review. Curr Res Transl Med. 2021; 69(4): 103304.

[299]

Clerico M, Dogliotti I, Aroldi A, et al. Post-transplant lymphoproliferative disease (PTLD) after allogeneic hematopoietic stem cell transplantation: biology and treatment options. J Clin Med. 2022; 11(24).

[300]

McKenna M, Epperla N, Ghobadi A, et al. Real-world evidence of the safety and survival with CD19 CAR-T cell therapy for relapsed/refractory solid organ transplant-related PTLD. Br J Haematol. 2023; 202(2): 248-255.

[301]

Liu JY, Zhang JM, Zhan HS, Sun LY, Wei L. EBV-specific cytotoxic T lymphocytes for refractory EBV-associated post-transplant lymphoproliferative disorder in solid organ transplant recipients: a systematic review. Transpl Int. 2021; 34(12): 2483-2493.

[302]

Fabrizio VA, Rodriguez-Sanchez MI, Mauguen A, et al. Adoptive therapy with CMV-specific cytotoxic T lymphocytes depends on baseline CD4+ immunity to mediate durable responses. Blood Adv. 2021; 5(2): 496-503.

[303]

Ke P, Bao X, Zhou J, et al. Donor CMV-specific cytotoxic T lymphocytes successfully treated drug-resistant cytomegalovirus encephalitis after allogeneic hematopoietic stem cell transplantation. Hematology. 2020; 25(1): 43-47.

[304]

Blyth E, Clancy L, Simms R, et al. Donor-derived CMV-specific T cells reduce the requirement for CMV-directed pharmacotherapy after allogeneic stem cell transplantation. Blood. 2013; 121(18): 3745-3758.

[305]

Zhang X, He J, Zhao K, et al. Mesenchymal stromal cells ameliorate chronic GVHD by boosting thymic regeneration in a CCR9-dependent manner in mice. Blood Adv. 2023; 7(18): 5359-5373.

[306]

Zhuoya W, Nannan Z, Aiping Z, et al. Human placenta derived mesenchymal stromal cells alleviate GVHD by promoting the generation of GSH and GST in PD-1(+)T cells. Cell Immunol. 2020; 352: 104083.

[307]

Geiger S, Ozay EI, Geumann U, et al. Alpha-1 antitrypsin-expressing mesenchymal stromal cells confer a long-term survival benefit in a mouse model of lethal GvHD. Mol Ther. 2019; 27(8): 1436-1451.

[308]

Proics E, David M, Mojibian M, et al. Preclinical assessment of antigen-specific chimeric antigen receptor regulatory T cells for use in solid organ transplantation. Gene Ther. 2023; 30(3-4): 309-322.

[309]

Descalzi-Montoya DB, Yang Z, Fanning S, et al. Cord blood-derived multipotent stem cells ameliorate in vitro/in vivo alloreactive responses, and this effect is associated with exosomal microvesicles in vitro. Transplant Cell Ther. 2024; 30(4): 396.e1-396.e14.

[310]

Sun X, He Q, Yang J, et al. Preventive and therapeutic effects of a novel JAK inhibitor SHR0302 in acute graft-versus-host disease. Cell Transplant. 2021; 30: 9636897211033778.

[311]

Chen Y, Yan G, Ma Y, et al. Combination of mesenchymal stem cells and FK506 prolongs heart allograft survival by inhibiting TBK1/IRF3-regulated-IFN-γ production. Immunol Lett. 2021; 238: 21-28.

[312]

Tuo L, Song H, Jiang D, Bai X, Song G. Mesenchymal stem cells transfected with anti-miRNA-204-3p inhibit acute rejection after heart transplantation by targeting C-X-C motif chemokine receptor 4 (CXCR4) in vitro. J Thorac Dis. 2021; 13(8): 5077-5092.

[313]

Lu X, Ru Y, Chu C, et al. Lentivirus-mediated IL-10-expressing bone marrow mesenchymal stem cells promote corneal allograft survival via upregulating lncRNA 003946 in a rat model of corneal allograft rejection. Theranostics. 2020; 10(18): 8446-8467.

[314]

Wang J, Ma Y, Wang J. miR-27a-5p inhibits acute rejection of liver transplantation in rats by inducing M2 polarization of Kupffer cells through the PI3K/Akt pathway. Cytokine. 2023; 165: 156085.

[315]

Chai H, Lei Z, Liu Y, et al. miR-505-5p alleviates acute rejection of liver transplantation by inhibiting Myd88 and inducing M2 polarizationof Kupffer cells. Acta Biochim Biophys Sin (Shanghai). 2022; 54(8): 1148-1158.

[316]

Morath C, Schmitt A, Kleist C, et al. Phase I trial of donor-derived modified immune cell infusion in kidney transplantation. J Clin Invest. 2020; 130(5): 2364-2376.

[317]

Guo H, Li B, Li N, et al. Exosomes: potential executors of IL-35 gene-modified adipose-derived mesenchymal stem cells in inhibiting acute rejection after heart transplantation. Scand J Immunol. 2022; 96(2): e13171.

[318]

Kong G, Chen Y, Liu Z, Wang Y, Li H, Guo C. Adenovirus-IL-10 relieves chronic rejection after mouse heart transplantation by inhibiting miR-155 and activating SOCS5. Int J Med Sci. 2023; 20(2): 172-185.

[319]

Shao B, Zhang JY, Ren SH, et al. Recombinant human IL-37 attenuates acute cardiac allograft rejection in mice. Cytokine. 2024; 179: 156598.

[320]

Lin M, Bhakdi SC, Tan D, et al. Lytic efficiency of immunosuppressive drug-resistant armoured T cells against circulating HBV-related HCC in whole blood. Immunother Adv. 2023; 3(1): ltad015.

[321]

Halden TAS, Kvitne KE, Midtvedt K, et al. Efficacy and safety of empagliflozin in renal transplant recipients with posttransplant diabetes mellitus. Diabetes Care. 2019; 42(6): 1067-1074.

[322]

Sánchez Fructuoso AI, Bedia Raba A, Banegas Deras E, et al. Sodium-glucose cotransporter-2 inhibitor therapy in kidney transplant patients with type 2 or post-transplant diabetes: an observational multicentre study. Clin Kidney J. 2023; 16(6): 1022-1034.

[323]

Thiruvengadam S, Hutchison B, Lim W, et al. Intensive monitoring for post-transplant diabetes mellitus and treatment with dipeptidyl peptidase-4 inhibitor therapy. Diabetes Metab Syndr. 2019; 13(3): 1857-1863.

[324]

Bae J, Kim Y, Cho Y, et al. Efficacy and safety of gemigliptin in post-transplant patients with type 2 diabetes mellitus. Transplant Proc. 2019; 51(10): 3444-3448.

[325]

Li L, Zhao H, Chen B, et al. FXR activation alleviates tacrolimus-induced post-transplant diabetes mellitus by regulating renal gluconeogenesis and glucose uptake. J Transl Med. 2019; 17(1): 418.

[326]

Thangavelu T, Lyden E, Shivaswamy V. A retrospective study of glucagon-like peptide 1 receptor agonists for the management of diabetes after transplantation. Diabetes Ther. 2020; 11(4): 987-994.

[327]

Singh P, Taufeeq M, Pesavento TE, Washburn K, Walsh D, Meng S. Comparison of the glucagon-like-peptide-1 receptor agonists dulaglutide and liraglutide for the management of diabetes in solid organ transplant: a retrospective study. Diabetes Obes Metab. 2020; 22(5): 879-884.

[328]

Delos Santos RB, Hagopian JC, Chen L, et al. Sitagliptin versus placebo to reduce the incidence and severity of posttransplant diabetes mellitus after kidney transplantation—a single-center, randomized, double-blind controlled trial. Transplantation. 2023; 107(5): 1180-1187.

[329]

Kuhl M, Binner C, Jozwiak J, et al. Treatment of hypercholesterolaemia with PCSK9 inhibitors in patients after cardiac transplantation. PLoS One. 2019; 14(1): e0210373.

[330]

Uyanik-Uenal K, Stoegerer-Lanzenberger M, Auersperg K, Aliabadi-Zuckermann A, Laufer G, Zuckermann A. Treatment of therapy-resistant hyperlipidaemia after heart transplant with PCSK9-inhibitors. J Heart Lung Transplant. 2019; 38(4): S213-S214. Supplement.

[331]

Tsuchimoto A, Masutani K, Ueki K, et al. Effect of renin-angiotensin system blockade on graft survival and cardiovascular disease in kidney transplant recipients: retrospective multicenter study in Japan. Clin Exp Nephrol. 2020; 24(4): 369-378.

[332]

Lim J-H, Kwon S, Seo YJ, et al. Cardioprotective effect of SGLT2 inhibitor in diabetic kidney transplant recipients: a multicenter propensity score matched study. Kidney Int Rep. 2024.

[333]

Alotaibi T, Nagib AM, Denewar A, et al. Inhibition of proprotein convertase subtilisin/kexin-9 after kidney transplant: single-center experience among patients with high cardiovascular risk. Exp Clin Transplant. 2024; 22(1): 315-322. Suppl.

[334]

Zou Y, Chen Z, Zhang X, et al. Targeting PCSK9 ameliorates graft vascular disease in mice by inhibiting NLRP3 inflammasome activation in vascular smooth muscle cells. Front Immunol. 2022; 13: 894789.

[335]

Birdwell KA, Decker B, Barbarino JM, et al. Clinical pharmacogenetics implementation consortium (CPIC) guidelines for CYP3A5 genotype and tacrolimus dosing. Clin Pharmacol Ther. 2015; 98(1): 19-24.

[336]

Cheng Y, Li H, Meng Y, et al. Effect of CYP3A5 polymorphism on the pharmacokinetics of tacrolimus and acute rejection in renal transplant recipients: experience at a single centre. Int J Clin Pract Suppl. 2015(183): 16-22.

[337]

Asempa TE, Rebellato LM, Hudson S, Briley K, Maldonado AQ. Impact of CYP3A5 genomic variances on clinical outcomes among African American kidney transplant recipients. Clin Transplant. 2018; 32(1).

[338]

Uesugi M, Kikuchi M, Shinke H, et al. Impact of cytochrome P450 3A5 polymorphism in graft livers on the frequency of acute cellular rejection in living-donor liver transplantation. Pharmacogenet Genomics. 2014; 24(7): 356-366.

[339]

Marco DN, Molina M, Guio AM, et al. Effects of CYP3A5 Genotype on tacrolimus pharmacokinetics and graft-versus-host disease incidence in allogeneic hematopoietic stem cell transplantation. Pharmaceuticals (Basel). 2024; 17(5).

[340]

Edinur HA, Manaf SM. Che Mat NF. Genetic barriers in transplantation medicine. World J Transplant. 2016; 6(3): 532-541.

[341]

Lan X, Zhang MM, Pu CL, et al. Impact of human leukocyte antigen mismatching on outcomes of liver transplantation: a meta-analysis. World J Gastroenterol. 2010; 16(27): 3457-3464.

[342]

Booth GS, Gehrie EA, Bolan CD, Savani BN. Clinical guide to ABO-incompatible allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2013; 19(8): 1152-1158.

[343]

Suárez-Alvarez B, López-Vázquez A, Gonzalez MZ, et al. The relationship of anti-MICA antibodies and MICA expression with heart allograft rejection. Am J Transplant. 2007; 7(7): 1842-1848.

[344]

Vakil MK, Mansoori Y, Al-Awsi GRL, et al. Individual genetic variability mainly of proinflammatory cytokines, cytokine receptors, and toll-like receptors dictates pathophysiology of COVID-19 disease. J Med Virol. 2022; 94(9): 4088-4096.

[345]

Dukat-Mazurek A, Bieniaszewska M, Hellmann A, Moszkowska G, Trzonkowski P. Association of cytokine gene polymorphisms with the complications of allogeneic haematopoietic stem cell transplantation. Hum Immunol. 2017; 78(11-12): 672-683.

[346]

Nair S, Dhodapkar MV. Natural killer T cells in cancer immunotherapy. Front Immunol. 2017; 8: 1178.

[347]

Gu Y, Hu Y, Hu K, et al. Rapamycin together with TGF-β1, IL-2 and IL-15 induces the generation of functional regulatory γδT cells from human peripheral blood mononuclear cells. J Immunol Methods. 2014; 402(1-2): 82-87.

[348]

Kaneko Y, Harada M, Kawano T, et al. Augmentation of Valpha14 NKT cell-mediated cytotoxicity by interleukin 4 in an autocrine mechanism resulting in the development of concanavalin A-induced hepatitis. J Exp Med. 2000; 191(1): 105-114.

[349]

Ito H, Ando K, Ishikawa T, et al. Role of Valpha14+ NKT cells in the development of Hepatitis B virus-specific CTL: activation of Valpha14+ NKT cells promotes the breakage of CTL tolerance. Int Immunol. 2008; 20(7): 869-879.

[350]

Moiseev IS, Babenko EV, Epifanovskaya OS, et al. High prevalence of CD3, NK, and NKT cells in the graft predicts adverse outcome after matched-related and unrelated transplantations with post transplantation cyclophosphamide. Bone Marrow Transplant. 2020; 55(3): 544-552.

[351]

Hodge G, Hodge S, Holmes-Liew CL, Reynolds PN, Holmes M. Histone deacetylase 2 is decreased in peripheral blood pro-inflammatory CD8+ T and NKT-like lymphocytes following lung transplant. Respirology. 2017; 22(2): 394-400.

[352]

Deseke M, Prinz I. Ligand recognition by the γδ TCR and discrimination between homeostasis and stress conditions. Cell Mol Immunol. 2020; 17(9): 914-924.

[353]

Xu L, Feng J, Xu X, et al. IL-17-producing γδT cells ameliorate intestinal acute graft-versus-host disease by recruitment of Gr-1(+)CD11b(+) myeloid-derived suppressor cells. Bone Marrow Transplant. 2021; 56(10): 2389-2399.

[354]

Malone F, Carper K, Reyes J, Li W. gammadeltaT cells are involved in liver transplant tolerance. Transplant Proc. 2009; 41(1): 233-235.

[355]

Kabelitz D, Serrano R, Kouakanou L, Peters C, Kalyan S. Cancer immunotherapy with γδ T cells: many paths ahead of us. Cell Mol Immunol. 2020; 17(9): 925-939.

[356]

Mirchandani AS, Besnard AG, Yip E, et al. Type 2 innate lymphoid cells drive CD4+ Th2 cell responses. J Immunol. 2014; 192(5): 2442-2448.

[357]

Chiossone L, Dumas PY, Vienne M, Vivier E. Natural killer cells and other innate lymphoid cells in cancer. Nat Rev Immunol. 2018; 18(11): 671-688.

[358]

Scheper W, van Dorp S, Kersting S, et al. γδT cells elicited by CMV reactivation after allo-SCT cross-recognize CMV and leukemia. Leukemia. 2013; 27(6): 1328-1338.

[359]

Robinette ML, Colonna M. Innate lymphoid cells and the MHC. Hla. 2016; 87(1): 5-11.

[360]

Bruchard M, Geindreau M, Perrichet A, et al. Recruitment and activation of type 3 innate lymphoid cells promote antitumor immune responses. Nat Immunol. 2022; 23(2): 262-274.

[361]

Pan Y, Yu Y, Wang X, Zhang T. Tumor-associated macrophages in tumor immunity. Front Immunol. 2020; 11: 583084.

[362]

Zhang W, Zhang Q, Yang N, et al. Crosstalk between IL-15Rα(+) tumor-associated macrophages and breast cancer cells reduces CD8(+) T cell recruitment. Cancer Commun (Lond). 2022; 42(6): 536-557.

[363]

Liang Y, Tan Y, Guan B, et al. Single-cell atlases link macrophages and CD8(+) T-cell subpopulations to disease progression and immunotherapy response in urothelial carcinoma. Theranostics. 2022; 12(18): 7745-7759.

[364]

Garnier AS, Planchais M, Riou J, et al. Pre-transplant CD45RC expression on blood T cells differentiates patients with cancer and rejection after kidney transplantation. PLoS One. 2019; 14(3): e0214321.

[365]

Greenfield HM, Gharib MI, Turner AJ, et al. The impact of monitoring Epstein-Barr virus PCR in paediatric bone marrow transplant patients: can it successfully predict outcome and guide intervention? Pediatr Blood Cancer. 2006; 47(2): 200-205.

[366]

Pai JA, Satpathy AT. High-throughput and single-cell T cell receptor sequencing technologies. Nat Methods. 2021; 18(8): 881-892.

[367]

Reguzova AY, Karpenko LI, Mechetina LV, Belyakov IM. Peptide-MHC multimer-based monitoring of CD8 T-cells in HIV-1 infection and AIDS vaccine development. Expert Rev Vaccines. 2015; 14(1): 69-84.

[368]

Zhang Z, Xiong D, Wang X, Liu H, Wang T. Mapping the functional landscape of T cell receptor repertoires by single-T cell transcriptomics. Nat Methods. 2021; 18(1): 92-99.

[369]

Sigdel TK, Fields PA, Liberto J, et al. Perturbations of the T-cell immune repertoire in kidney transplant rejection. Front Immunol. 2022; 13: 1012042.

[370]

Pauken KE, Lagattuta KA, Lu BY, et al. TCR-sequencing in cancer and autoimmunity: barcodes and beyond. Trends Immunol. 2022; 43(3): 180-194.

[371]

Bentzen AK, Marquard AM, Lyngaa R, et al. Large-scale detection of antigen-specific T cells using peptide-MHC-I multimers labeled with DNA barcodes. Nat Biotechnol. 2016; 34(10): 1037-1045.

[372]

Kohut TJ, Barandiaran JF, Keating BJ. Genomics and liver transplantation: genomic biomarkers for the diagnosis of acute cellular rejection. Liver Transpl. 2020; 26(10): 1337-1350.

[373]

Margolskee E, Jobanputra V, Jain P, et al. Genetic landscape of T-and NK-cell post-transplant lymphoproliferative disorders. Oncotarget. 2016; 7(25): 37636-37648.

[374]

Zhi Y, Li M, Lv G. Into the multi-omics era: progress of T cells profiling in the context of solid organ transplantation. Front Immunol. 2023; 14: 1058296.

[375]

Peters FS, Peeters AMA, van den Bosch TPP, et al. Disrupted regulation of serpinB9 in circulating T cells is associated with an increased risk for post-transplant skin cancer. Clin Exp Immunol. 2019; 197(3): 341-351.

[376]

Nguyen TH, Bird NL, Grant EJ, et al. Maintenance of the EBV-specific CD8(+) TCRαβ repertoire in immunosuppressed lung transplant recipients. Immunol Cell Biol. 2017; 95(1): 77-86.

[377]

Geiger R, Rieckmann JC, Wolf T, et al. L-arginine modulates T cell metabolism and enhances survival and anti-tumor activity. Cell. 2016; 167(3): 829-842. e13.

[378]

Matias MI, Yong CS, Foroushani A, et al. Regulatory T cell differentiation is controlled by αKG-induced alterations in mitochondrial metabolism and lipid homeostasis. Cell Rep. 2021; 37(5): 109911.

[379]

Tellez J, Jaing C, Wang J, Green R, Chen M. Detection of Epstein-Barr virus (EBV) in human lymphoma tissue by a novel microbial detection array. Biomark Res. 2014; 2(1): 24.

[380]

Anthony BA, Hadley GA. Induction of graft-versus-host disease and in vivo T cell monitoring using an MHC-matched murine model. J Vis Exp. 2012(66):e3697.

[381]

Mohri T, Ikura Y, Hirakoso A, et al. Classical Hodgkin lymphoma type post-transplant lymphoproliferative disorder in a kidney transplant recipient: a diagnostic pitfall. Int J Hematol. 2018; 108(2): 218-227.

[382]

Ma BM, Elefant N, Tedesco M, et al. Developing a genetic testing panel for evaluation of morbidities in kidney transplant recipients. Kidney Int. 2024; 106(1): 115-125.

[383]

Hu H, Kwun J, Aizenstein BD, Knechtle SJ. Noninvasive detection of acute and chronic injuries in human renal transplant by elevation of multiple cytokines/chemokines in urine. Transplantation. 2009; 87(12): 1814-1820.

[384]

Reikvam H, Bruserud Ø, Hatfield KJ. Pretransplant systemic metabolic profiles in allogeneic hematopoietic stem cell transplant recipients—identification of patient subsets with increased transplant-related mortality. Transplant Cell Ther. 2023; 29(6): 375.e1-375.e14.

[385]

Hruba P, Klema J, Le AV, et al. Novel transcriptomic signatures associated with premature kidney allograft failure. EBioMedicine. 2023; 96: 104782.

[386]

Bontha SV, Maluf DG, Mueller TF, Mas VR. Systems biology in kidney transplantation: the application of multi-omics to a complex model. Am J Transplant. 2017; 17(1): 11-21.

[387]

Sui W, Lin H, Peng W, et al. Molecular dysfunctions in acute rejection after renal transplantation revealed by integrated analysis of transcription factor, microRNA and long noncoding RNA. Genomics. 2013; 102(4): 310-322.

[388]

Briceño J, Ayllón MD, Ciria R. Machine-learning algorithms for predicting results in liver transplantation: the problem of donor-recipient matching. Curr Opin Organ Transplant. 2020; 25(4): 406-411.

[389]

Guijo-Rubio D, Briceño J, Gutiérrez PA, Ayllón MD, Ciria R, Hervás-Martínez C. Statistical methods versus machine learning techniques for donor-recipient matching in liver transplantation. PLoS One. 2021; 16(5): e0252068.

[390]

Briceño J, Cruz-Ramírez M, Prieto M, et al. Use of artificial intelligence as an innovative donor-recipient matching model for liver transplantation: results from a multicenter Spanish study. J Hepatol. 2014; 61(5): 1020-1028.

[391]

Ayllón MD, Ciria R, Cruz-Ramírez M, et al. Validation of artificial neural networks as a methodology for donor-recipient matching for liver transplantation. Liver Transpl. 2018; 24(2): 192-203.

[392]

Ayers B, Sandholm T, Gosev I, Prasad S, Kilic A. Using machine learning to improve survival prediction after heart transplantation. J Card Surg. 2021; 36(11): 4113-4120.

[393]

Miller R, Tumin D, Cooper J, Hayes D Jr, Tobias JD. Prediction of mortality following pediatric heart transplant using machine learning algorithms. Pediatr Transplant. 2019; 23(3): e13360.

[394]

Tian D, Yan HJ, Huang H, et al. Machine learning-based prognostic model for patients after lung transplantation. JAMA Netw Open. 2023; 6(5): e2312022.

[395]

Chandra G, Wang J, Siirtola P, Röning J. Leveraging machine learning for predicting acute graft-versus-host disease grades in allogeneic hematopoietic cell transplantation for T-cell prolymphocytic leukaemia. BMC Med Res Methodol. 2024; 24(1): 112.

[396]

Tanaka T, Voigt MD. Decision tree analysis to stratify risk of de novo non-melanoma skin cancer following liver transplantation. J Cancer Res Clin Oncol. 2018; 144(3): 607-615.

[397]

Jo SJ, Park JB, Lee KW. Prediction of very early subclinical rejection with machine learning in kidney transplantation. Sci Rep. 2023; 13(1): 22387.

[398]

Zare A, Zare MA, Zarei N, et al. A neural network approach to predict acute allograft rejection in liver transplant recipients using routine laboratory data. Research article. Hepat Mon. 2017; 17(12): e55092.

[399]

Ram S, Verleden SE, Kumar M, et al. Computed tomography-based machine learning for donor lung screening before transplantation. J Heart Lung Transplant. 2024; 43(3): 394-402.

[400]

El Hage A, Dormond O. Combining mTOR inhibitors and T cell-based immunotherapies in cancer treatment. Cancers (Basel). 2021; 13(6).

[401]

Havenith SH, Yong SL, van Donselaar-van der Pant KA, van Lier RA, ten Berge IJ, Bemelman FJ. Everolimus-treated renal transplant recipients have a more robust CMV-specific CD8+ T-cell response compared with cyclosporine-or mycophenolate-treated patients. Transplantation. 2013; 95(1): 184-191.

[402]

Rozenbaum M, Meir A, Aharony Y, et al. Gamma-Delta CAR-T cells show CAR-directed and independent activity against leukemia. Front Immunol. 2020; 11: 1347.

[403]

Sebestyen Z, Prinz I, Déchanet-Merville J, Silva-Santos B, Kuball J. Translating gammadelta (γδ) T cells and their receptors into cancer cell therapies. Nat Rev Drug Discov. 2020; 19(3): 169-184.

[404]

Godder KT, Henslee-Downey PJ, Mehta J, et al. Long term disease-free survival in acute leukemia patients recovering with increased gammadelta T cells after partially mismatched related donor bone marrow transplantation. Bone Marrow Transplant. 2007; 39(12): 751-757.

[405]

Xuan L, Wu X, Qiu D, et al. Regulatory γδ T cells induced by G-CSF participate in acute graft-versus-host disease regulation in G-CSF-mobilized allogeneic peripheral blood stem cell transplantation. J Transl Med. 2018; 16(1): 144.

[406]

Ye W, Kong X, Zhang W, Weng Z, Wu X. The roles of γδ T cells in hematopoietic stem cell transplantation. Cell Transplant. 2020; 29: 963689720966980.

[407]

Gaballa MR, Ramos CA. Cellular immunotherapy in lymphoma: beyond CART cells. Curr Treat Options Oncol. 2020; 21(3): 21.

[408]

Bajwa G, Lanz I, Cardenas M, Brenner MK, Arber C. Transgenic CD8αβ co-receptor rescues endogenous TCR function in TCR-transgenic virus-specific T cells. J Immunother Cancer. 2020; 8(2).

RIGHTS & PERMISSIONS

2024 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.

AI Summary AI Mindmap
PDF

175

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/