The reactive stroma response regulates the immune landscape in prostate cancer

Abstract

Prostate cancer remains the most commonly diagnosed and the second leading cause of cancer-related deaths in men in the United States. The neoplastic transformation of prostate epithelia, concomitant with modulations in the stromal compartment, known as reactive stromal response, is critical for the growth, development, and progression of prostate cancer. Reactive stroma typifies an emergent response to disrupted tissue homeostasis commonly observed in wound repair and pathological conditions such as cancer. Despite the significance of reactive stroma in prostate cancer pathobiology, our understanding of the ontogeny, phenotypic and functional heterogeneity, and reactive stromal regulation of the immune microenvironment in prostate cancer remains limited. Traditionally characterized to have an immunologically "cold" tumor microenvironment, prostate cancer presents significant challenges for advancing immunotherapy compared to other solid tumors. This review explores the detrimental role of reactive stroma in prostate cancer, particularly its immunomodulatory function. Understanding the molecular characteristics and dynamic transcriptional program of the reactive stromal populations in tandem with tumor progression could offer insights into enhancing immunotherapy efficacy against prostate cancer.

Keywords

Prostate cancer / emergent/repair biology / reactive stroma / tumor microenvironment / immune landscape / immunotherapy

References

[1] Cunha GR,Cooke PS.The endocrinology and developmental biology of the prostate.Endocr Rev1987;8:338-62

[2] Kumar VL.Prostate gland: structure, functions and regulation.Int Urol Nephrol1995;27:231-43

[3] Singh O. Anatomy, abdomen and pelvis, prostate. Treasure Island: StatPearls; 2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK540987/ [Last accessed on 22 Jul 2024]

[4] Rawla P.Epidemiology of prostate cancer.World J Oncol2019;10:63-89 PMCID:PMC6497009

[5] Schrecengost R.Molecular pathogenesis and progression of prostate cancer.Semin Oncol2013;40:244-58 PMCID:PMC3727396

[6] Siegel RL,Jemal A.Cancer statistics, 2024.CA Cancer J Clin2024;74:12-49

[7] Shore ND,Pienta KJ,King MT.Biochemical recurrence in patients with prostate cancer after primary definitive therapy: treatment based on risk stratification.Prostate Cancer Prostatic Dis2024;27:192-201 PMCID:PMC11096125

[8] Krušlin B,Tomas D.Prostate cancer stroma: an important factor in cancer growth and progression.Bosn J Basic Med Sci2015;15:1-8 PMCID:PMC4469930

[9] Levesque C.Cellular constituents of the prostate stroma: key contributors to prostate cancer progression and therapy resistance.CSH Perspect Med2018;8:a030510 PMCID:PMC5681439

[10] Pederzoli F,Pakula H,Nuzzo PV.Stromal cells in prostate cancer pathobiology: friends or foes?.Br J Cancer2023;128:930-9 PMCID:PMC10006214

[11] Barron DA.The reactive stroma microenvironment and prostate cancer progression.Endocr Relat Cancer2012;19:R187-204 PMCID:PMC3716392

[12] Davey RA.Androgen receptor structure, function and biology: from bench to bedside.Clin Biochem Rev2016;37:3-15 PMCID:PMC4810760

[13] Wen S,Tian J,Niu Y.Stromal androgen receptor roles in the development of normal prostate, benign prostate hyperplasia, and prostate cancer.Am J Pathol2015;185:293-301 PMCID:PMC4305176

[14] Cunha GR.Epithelio-mesenchymal interactions in primordial gland structures which become responsive to androgenic stimulation.Anat Rec1972;172:179-95

[15] Schauer IG.The functional role of reactive stroma in benign prostatic hyperplasia.Differentiation2011;82:200-10 PMCID:PMC3179838

[16] Schauer IG,Tuxhorn JA,Rowley DR.Elevated epithelial expression of interleukin-8 correlates with myofibroblast reactive stroma in benign prostatic hyperplasia.Urology2008;72:205-13 PMCID:PMC2528841

[17] Tuxhorn JA,Smith MJ,Dang TD.Reactive stroma in human prostate cancer: induction of myofibroblast phenotype and extracellular matrix remodeling.Clin Cancer Res2002;8:2912-23

[18] Tuxhorn JA,Rowley DR.Reactive stroma in prostate cancer progression.J Urol2001;166:2472-83

[19] Kai F,Weaver VM.The extracellular matrix modulates the metastatic journey.Dev Cell2019;49:332-46 PMCID:PMC6527347

[20] Valkenburg KC,Pienta KJ.Targeting the tumour stroma to improve cancer therapy.Nat Rev Clin Oncol2018;15:366-81 PMCID:PMC5960434

[21] Puré E.Can targeting stroma pave the way to enhanced antitumor immunity and immunotherapy of solid tumors?.Cancer Immunol Res2016;4:269-78 PMCID:PMC5452418

[22] Quail DF.Microenvironmental regulation of tumor progression and metastasis.Nat Med2013;19:1423-37 PMCID:PMC3954707

[23] Xiao Z,Huang L.Desmoplastic stroma restricts T cell extravasation and mediates immune exclusion and immunosuppression in solid tumors.Nat Commun2023;14:5110 PMCID:PMC10444764

[24] Zhang FF,Xie Y.Epitope-based minigene vaccine targeting fibroblast activation protein α induces specific immune responses and anti-tumor effects in 4 T1 murine breast cancer model.Int Immunopharmacol2022;112:109237

[25] Gorbach IN.[Detection of leukocyte sensitization to tuberculosis mycobacterial antigens in newborns by the method of migration suppression in vitro].Vopr Okhr Materin Det1976;21:66-8

[26] Giacomini A,Rezzola S.The FGF/FGFR system in the physiopathology of the prostate gland.Physiol Rev2021;101:569-610

[27] Cunha GR.Mesenchymal-epithelial interactions: past, present, and future.Differentiation2008;76:578-86

[28] Roberson KM,Chang GC.Isolation and characterization of a novel human prostatic stromal cell culture: DuK50.In Vitro Cell Dev Biol Anim1995;31:840-5

[29] Webber MM,Thraves PS.A human prostatic stromal myofibroblast cell line WPMY-1: a model for stromal-epithelial interactions in prostatic neoplasia.Carcinogenesis1999;20:1185-92

[30] Simons BW,Huang Z.Wnt signaling though beta-catenin is required for prostate lineage specification.Dev Biol2012;371:246-55 PMCID:PMC3472417

[31] Farnsworth WE.Prostate stroma: physiology.Prostate1999;38:60-72

[32] Mostofi FK,Davis CJ.A pathologist's view of prostatic carcinoma.Cancer1993;71:906-32

[33] Steukers L,Vandekerckhove AP,Nauwynck HJ.Diverse microbial interactions with the basement membrane barrier.Trends Microbiol2012;20:147-55 PMCID:PMC7127156

[34] Brekken RA.Extracellular matrix in tumor biology. In: Biology of extracellular matrix. Cham: Springer International Publishing; 2017.

[35] Welén K.Androgens, aging, and prostate health.Rev Endocr Metab Disord2022;23:1221-31 PMCID:PMC9789017

[36] Stanworth RD.Testosterone for the aging male; current evidence and recommended practice.Clin Interv Aging2008;3:25-44

[37] Prins GS,Birch L.The role of estrogens in normal and abnormal development of the prostate gland.Ann N Y Acad Sci2006;1089:1-13 PMCID:PMC2276871

[38] Shapiro E,Masch RJ,Wilson EL.Immunolocalization of estrogen receptor alpha and beta in human fetal prostate.J Urol2005;174:2051-3

[39] Prins GS.The role of estrogens and estrogen receptors in normal prostate growth and disease.Steroids2008;73:233-44 PMCID:PMC2262439

[40] Coffey DS.Clinical and experimental studies of benign prostatic hyperplasia.Urol Clin North Am1990;17:461-75

[41] Vickman RE,Moline DC,Thumbikat P.The role of the androgen receptor in prostate development and benign prostatic hyperplasia: a review.Asian J Urol2020;7:191-202 PMCID:PMC7385520

[42] Schulze H.Histological localization of estrogen receptors in normal and diseased human prostates by immunocytochemistry.Prostate1990;16:331-43

[43] Schulze H.Immunocytochemical localization of estrogen receptors in the normal male and female canine urinary tract and prostate.Endocrinology1987;121:1773-83

[44] Prins GS.Neonatal estrogen exposure up-regulates estrogen receptor expression in the developing and adult rat prostate lobes.Endocrinology1997;138:1801-9

[45] Yu Y,Xie N.Expression and function of the progesterone receptor in human prostate stroma provide novel insights to cell proliferation control.J Clin Endocrinol Metab2013;98:2887-96 PMCID:PMC4078099

[46] Arora VK,Murali R.Glucocorticoid receptor confers resistance to antiandrogens by bypassing androgen receptor blockade.Cell2013;155:1309-22 PMCID:PMC3932525

[47] Tuong ZK,Berry B.Resolving the immune landscape of human prostate at a single-cell level in health and cancer.Cell Rep2021;37:110132 PMCID:PMC8721283

[48] Henry GH,Joseph DB.A cellular anatomy of the normal adult human prostate and prostatic urethra.Cell Rep2018;25:3530-3542.e5 PMCID:PMC6411034

[49] Mass E,Farlik M.Specification of tissue-resident macrophages during organogenesis.Science2016;353:aaf4238 PMCID:PMC5066309

[50] Costello LC.A comprehensive review of the role of zinc in normal prostate function and metabolism; and its implications in prostate cancer.Arch Biochem Biophys2016;611:100-12 PMCID:PMC5083243

[51] Singh KK,Franklin RB.Mitochondrial aconitase and citrate metabolism in malignant and nonmalignant human prostate tissues.Mol Cancer2006;5:14 PMCID:PMC1484490

[52] Ginhoux F.Tissue-resident macrophage ontogeny and homeostasis.Immunity2016;44:439-49

[53] Cannarella R,Barbagallo F,Calogero AE.Endocrinology of the aging prostate: current concepts.Front Endocrinol2021;12:554078 PMCID:PMC7939072

[54] Feldman HA,Derby CA.Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study.J Clin Endocrinol Metab2002;87:589-98

[55] O'Donnell AB,McKinlay JB.The health of normally aging men: The massachusetts male aging study (1987-2004).Exp Gerontol2004;39:975-84

[56] Huhtaniemi I.Late-onset hypogonadism: current concepts and controversies of pathogenesis, diagnosis and treatment.Asian J Androl2014;16:192-202 PMCID:PMC3955328

[57] Rastrelli G,Corona G.Testosterone and benign prostatic hyperplasia.Sex Med Rev2019;7:259-71

[58] Vignozzi L,Santi R.Antiinflammatory effect of androgen receptor activation in human benign prostatic hyperplasia cells.J Endocrinol2012;214:31-43

[59] Ho CH,Yu HJ.Testosterone suppresses uropathogenic escherichia coli invasion and colonization within prostate cells and inhibits inflammatory responses through JAK/STAT-1 signaling pathway.PLoS One2017;12:e0180244 PMCID:PMC5493373

[60] Quintar AA,Taboga SR.The mongolian gerbil (meriones unguiculatus) as a model for inflammation-promoted prostate carcinogenesis.Cell Biol Int2017;41:1234-8

[61] Cohen PG.Obesity in men: the hypogonadal-estrogen receptor relationship and its effect on glucose homeostasis.Med Hypotheses2008;70:358-60

[62] Yang Y,Hu S.Estrogen and G protein-coupled estrogen receptor accelerate the progression of benign prostatic hyperplasia by inducing prostatic fibrosis.Cell Death Dis2022;13:533 PMCID:PMC9174491

[63] Ellem SJ.Aromatase and regulating the estrogen: androgen ratio in the prostate gland.J Steroid Biochem Mol Biol2010;118:246-51

[64] Rebbeck TR.Prostate cancer disparities by race and ethnicity: from nucleotide to neighborhood.Cold Spring Harb Perspect Med2018;8:a030387 PMCID:PMC6120694

[65] Siegel RL,Fuchs HE.Cancer statistics, 2021.CA Cancer J Clin2021;71:7-33

[66] Chowdhury-Paulino IM,Vince R Jr,George DJ.Racial disparities in prostate cancer among black men: epidemiology and outcomes.Prostate Cancer Prostatic Dis2022;25:397-402 PMCID:PMC8888766

[67] Hinata N.Racial differences in prostate cancer characteristics and cancer-specific mortality: an overview.World J Mens Health2022;40:217-27 PMCID:PMC8987139

[68] Rohrmann S,Rifai N.Serum estrogen, but not testosterone, levels differ between black and white men in a nationally representative sample of Americans.J Clin Endocrinol Metab2007;92:2519-25

[69] Henderson BE,Ross RK,Judd HL.The early in utero oestrogen and testosterone environment of blacks and whites: potential effects on male offspring.Br J Cancer1988;57:216-8 PMCID:PMC2246431

[70] Platz EA.The epidemiology of sex steroid hormones and their signaling and metabolic pathways in the etiology of prostate cancer.J Steroid Biochem Mol Biol2004;92:237-53

[71] Giusti RM,Hatch EE.Diethylstilbestrol revisited: a review of the long-term health effects.Ann Intern Med1995;122:778-88

[72] Fox JJ,Navarro HI,Shou BL.Highly multiplexed immune profiling throughout adulthood reveals kinetics of lymphocyte infiltration in the aging mouse prostate.Aging2023;15:3356-80 PMCID:PMC10449296

[73] Khan D.The immune system is a natural target for estrogen action: opposing effects of estrogen in two prototypical autoimmune diseases.Front Immunol2015;6:635 PMCID:PMC4701921

[74] Eifert C.From cancer genomes to oncogenic drivers, tumour dependencies and therapeutic targets.Nat Rev Cancer2012;12:572-8

[75] Dotto GP.Multifocal epithelial tumors and field cancerization: stroma as a primary determinant.J Clin Invest2014;124:1446-53 PMCID:PMC3973113

[76] Cunha GR,Wang YZ.Role of the stromal microenvironment in carcinogenesis of the prostate.Int J Cancer2003;107:1-10

[77] Cunha GR,Wang YZ.Role of stroma in carcinogenesis of the prostate.Differentiation2002;70:473-85

[78] Wang Y,Zhang B.A human prostatic epithelial model of hormonal carcinogenesis.Cancer Res2001;61:6064-72

[79] Ricke WA,Ricke EA.Steroid hormones stimulate human prostate cancer progression and metastasis.Int J Cancer2006;118:2123-31

[80] Hayward SW,Cao M.Malignant transformation in a nontumorigenic human prostatic epithelial cell line.Cancer Res2001;61:8135-42

[81] Hu B,Harewood L.Multifocal epithelial tumors and field cancerization from loss of mesenchymal CSL signaling.Cell2012;149:1207-20 PMCID:PMC3578441

[82] Salem AF,Whitaker-Menezes D.Cigarette smoke metabolically promotes cancer, via autophagy and premature aging in the host stromal microenvironment.Cell Cycle2013;12:818-25 PMCID:PMC3610729

[83] Yoshimoto S,Atarashi K.Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome.Nature2013;499:97-101

[84] Berglund E,Schultz N.Spatial maps of prostate cancer transcriptomes reveal an unexplored landscape of heterogeneity.Nat Commun2018;9:2419 PMCID:PMC6010471

[85] Kwon OJ,Li Y.Functional heterogeneity of mouse prostate stromal cells revealed by single-cell RNA-Seq.iScience2019;13:328-38 PMCID:PMC6423355

[86] Huet E,Nguyen HQ.Stroma in normal and cancer wound healing.FEBS J2019;286:2909-20

[87] Varga J,Phan SH. Fibrosis research: methods and protocols. Berlin: Springer; 2008.

[88] Clark RAF.The molecular and cellular biology of wound repair. New York: Plenum Press;1996

[89] Schäfer M.Cancer as an overhealing wound: an old hypothesis revisited.Nat Rev Mol Cell Biol2008;9:628-38

[90] Haddow A.Molecular repair, wound healing, and carcinogenesis: tumor production a possible overhealing? Amsterdam: Elsevier; 1973. pp. 181-234.

[91] Langley RR.The seed and soil hypothesis revisited--the role of tumor-stroma interactions in metastasis to different organs.Int J Cancer2011;128:2527-35 PMCID:PMC3075088

[92] Plava J,Burikova M,Kucerova L.Recent advances in understanding tumor stroma-mediated chemoresistance in breast cancer.Mol Cancer2019;18:67 PMCID:PMC6441200

[93] Mesker WE,Szuhai K.The carcinoma-stromal ratio of colon carcinoma is an independent factor for survival compared to lymph node status and tumor stage.Cell Oncol2007;29:387-98 PMCID:PMC4617992

[94] Almangush A,Troiano G.Clinical significance of tumor-stroma ratio in head and neck cancer: a systematic review and meta-analysis.BMC Cancer2021;21:480 PMCID:PMC8086072

[95] He R,Liu B.The prognostic value of tumor-stromal ratio combined with TNM staging system in esophagus squamous cell carcinoma.J Cancer2021;12:1105-14 PMCID:PMC7797665

[96] Zhu Y,Qian Y,Wang Z.Prognostic value of tumor-stroma ratio in rectal cancer: a systematic review and meta-analysis.Front Oncol2021;11:685570 PMCID:PMC8187802

[97] Ruder S,Ding Y.Development and validation of a quantitative reactive stroma biomarker (qRS) for prostate cancer prognosis.Hum Pathol2022;122:84-91 PMCID:PMC9832989

[98] Ayala G,Wheeler TM.Reactive stroma as a predictor of biochemical-free recurrence in prostate cancer.Clin Cancer Res2003;9:4792-801

[99] Tran LL,Thomas R.ELF3 mediates IL-1α induced differentiation of mesenchymal stem cells to inflammatory iCAFs.Stem Cells2021;39:1766-77 PMCID:PMC8963131

[100] Olumi AF,Hayward SW,Tlsty TD.Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium.Cancer Res1999;59:5002-11 PMCID:PMC3300837

[101] Hayashi N.Mesenchyme-induced changes in the neoplastic characteristics of the Dunning prostatic adenocarcinoma.Cancer Res1991;51:4924-30

[102] Proia DA.Stroma: tumor agonist or antagonist.Cell Cycle2005;4:1022-5

[103] Mun JY,Lee JH.Dual relationship between stromal cells and immune cells in the tumor microenvironment.Front Immunol2022;13:864739 PMCID:PMC9019709

[104] Sanjabi S,Li MO.Regulation of the immune response by TGF-β: from conception to autoimmunity and infection.Cold Spring Harb Perspect Biol2017;9:a022236 PMCID:PMC5453394

[105] Zhang F,Wang X.TGF-β induces M2-like macrophage polarization via SNAIL-mediated suppression of a pro-inflammatory phenotype.Oncotarget2016;7:52294-306 PMCID:PMC5239552

[106] Penn JW,Rolfe KJ.The role of the TGF-beta family in wound healing, burns and scarring: a review.Int J Burns Trauma2012;2:18-28

[107] Zhang Y,Wang XF.TGF-β family signaling in the control of cell proliferation and survival.Cold Spring Harb Perspect Biol2017;9:a022145 PMCID:PMC5378054

[108] Xu J,Derynck R.TGF-beta-induced epithelial to mesenchymal transition.Cell Res2009;19:156-72 PMCID:PMC4720263

[109] Farooq M,Kim MS.The role of fibroblast growth factor (FGF) signaling in tissue repair and regeneration.Cells2021;10:3242 PMCID:PMC8622657

[110] Pierce GF,Altrock BW,Thomason A.Role of platelet-derived growth factor in wound healing.J Cell Biochem1991;45:319-26

[111] Diller RB.The role of the extracellular matrix (ECM) in wound healing: a review.Biomimetics2022;7:87 PMCID:PMC9326521

[112] Rodriguez-Pascual F.Lysyl oxidases: functions and disorders.J Glaucoma2018;27 Suppl 1:S15-9

[113] Wang LC,Scholler J.Targeting fibroblast activation protein in tumor stroma with chimeric antigen receptor T cells can inhibit tumor growth and augment host immunity without severe toxicity.Cancer Immunol Res2014;2:154-66 PMCID:PMC4007316

[114] Nissen NI,Willumsen N.Collagens and cancer associated fibroblasts in the reactive stroma and its relation to cancer biology.J Exp Clin Cancer Res2019;38:115 PMCID:PMC6404286

[115] Henke E,Ergün S.Extracellular matrix in the tumor microenvironment and its impact on cancer therapy.Front Mol Biosci2019;6:160 PMCID:PMC7025524

[116] Hughes CC.Endothelial-stromal interactions in angiogenesis.Curr Opin Hematol2008;15:204-9 PMCID:PMC6606556

[117] Nishida N,Nishida T,Kojiro M.Angiogenesis in cancer.Vasc Health Risk Manag2006;2:213-9 PMCID:PMC1993983

[118] Li Y,Li XF.Hypoxia and the tumor microenvironment.Technol Cancer Res Treat2021;20:15330338211036304 PMCID:PMC8358492

[119] Zhang Y,Brekken RA.Perspectives on hypoxia signaling in tumor stroma.Cancers2021;13:3070 PMCID:PMC8234221

[120] Crola Da Silva C,Paprocka M.Selective human endothelial cell activation by chemokines as a guide to cell homing.Immunology2009;126:394-404 PMCID:PMC2669820

[121] Crowley T,Clark AR.Stroma: the forgotten cells of innate immune memory.Clin Exp Immunol2018;193:24-36 PMCID:PMC6038004

[122] Jiang Z,Li L.Pericytes in the tumor microenvironment.Cancer Lett2023;556:216074

[123] Thomas H,Mills SJ.The importance of pericytes in healing: wounds and other pathologies.Int J Mol Sci2017;18:1129 PMCID:PMC5485953

[124] Paiva AE,Guerra DAP.Pericytes in the premetastatic niche.Cancer Res2018;78:2779-86 PMCID:PMC6044472

[125] Kirk T,Rognoni E.Fibroblast memory in development, homeostasis and disease.Cells2021;10:2840 PMCID:PMC8616330

[126] Netea MG,van der Meer JW.Trained immunity: a memory for innate host defense.Cell Host Microbe2011;9:355-61

[127] Wang T,Dusi S."Open Sesame" to the complexity of pattern recognition receptors of myeloid-derived suppressor cells in cancer.Front Immunol2023;14:1130060 PMCID:PMC9992799

[128] Akira S,Takeuchi O.Pathogen recognition and innate immunity.Cell2006;124:783-801

[129] Netea MG.Trained immunity: an ancient way of remembering.Cell Host Microbe2017;21:297-300

[130] Dakin SG,Al-Mossawi MH.Persistent stromal fibroblast activation is present in chronic tendinopathy.Arthritis Res Ther2017;19:16 PMCID:PMC5264298

[131] Klein K,Karouzakis E.The epigenetic architecture at gene promoters determines cell type-specific LPS tolerance.J Autoimmun2017;83:122-33

[132] Sohn C,Qiao Y,Ivashkiv LB.Prolonged tumor necrosis factor α primes fibroblast-like synoviocytes in a gene-specific manner by altering chromatin.Arthritis Rheumatol2015;67:86-95 PMCID:PMC4455921

[133] Koch SR,Hellman J,Stark RJ.Potentiation and tolerance of toll-like receptor priming in human endothelial cells.Transl Res2017;180:53-67.e4 PMCID:PMC5253081

[134] Naik S,Gomez NC.Author correction: inflammatory memory sensitizes skin epithelial stem cells to tissue damage.Nature2018;560:E2

[135] Ara T,Hirai K.Human gingival fibroblasts are critical in sustaining inflammation in periodontal disease.J Periodontal Res2009;44:21-7

[136] Lee A,Grigoriev G.Tumor necrosis factor α induces sustained signaling and a prolonged and unremitting inflammatory response in rheumatoid arthritis synovial fibroblasts.Arthritis Rheum2013;65:928-38 PMCID:PMC3618592

[137] Springer TA.Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm.Cell1994;76:301-14

[138] Wolff B,Middleton J.Endothelial cell "memory" of inflammatory stimulation: human venular endothelial cells store interleukin 8 in Weibel-Palade bodies.J Exp Med1998;188:1757-62 PMCID:PMC2212526

[139] Bonfanti R,Furie B.PADGEM (GMP140) is a component of Weibel-Palade bodies of human endothelial cells.Blood1989;73:1109-12

[140] McEver RP,Moore KL,Bainton DF.GMP-140, a platelet alpha-granule membrane protein, is also synthesized by vascular endothelial cells and is localized in Weibel-Palade bodies.J Clin Invest1989;84:92-9 PMCID:PMC303957

[141] Zimmerman GA,Mehra M.Endothelial cell-associated platelet-activating factor: a novel mechanism for signaling intercellular adhesion.J Cell Biol1990;110:529-40 PMCID:PMC2116010

[142] Séguin C,Spokes KC.Priming effect of homocysteine on inducible vascular cell adhesion molecule-1 expression in endothelial cells.Biomed Pharmacother2008;62:395-400 PMCID:PMC5378488

[143] Ceriello A,Thorpe JE.Clinical review 2: the "metabolic memory": is more than just tight glucose control necessary to prevent diabetic complications?.J Clin Endocrinol Metab2009;94:410-5

[144] Testa R,Prattichizzo F,De Nigris V.The "Metabolic Memory" theory and the early treatment of hyperglycemia in prevention of diabetic complications.Nutrients2017;9:437 PMCID:PMC5452167

[145] Yao Y,Hu C.Endothelial cell metabolic memory causes cardiovascular dysfunction in diabetes.Cardiovasc Res2022;118:196-211

[146] Muhl L,Leptidis S.Single-cell analysis uncovers fibroblast heterogeneity and criteria for fibroblast and mural cell identification and discrimination.Nat Commun2020;11:3953 PMCID:PMC7414220

[147] Amersfoort J,Carmeliet P.Immunomodulation by endothelial cells - partnering up with the immune system?.Nat Rev Immunol2022;22:576-88 PMCID:PMC8920067

[148] Yeo SY,Shin D,Cho KH.A positive feedback loop bi-stably activates fibroblasts.Nat Commun2018;9:3016 PMCID:PMC6070563

[149] Wynn TA.Cellular and molecular mechanisms of fibrosis.J Pathol2008;214:199-210 PMCID:PMC2693329

[150] Rosenberg SA.Raising the bar: the curative potential of human cancer immunotherapy.Sci Transl Med2012;4:127ps8 PMCID:PMC6292198

[151] Lin R,Zheng J.Chronic inflammation-associated genomic instability paves the way for human esophageal carcinogenesis.Oncotarget2016;7:24564-71 PMCID:PMC5029723

[152] Hibino S,Kasahara H.Inflammation-induced tumorigenesis and metastasis.Int J Mol Sci2021;22:5421 PMCID:PMC8196678

[153] Bockerstett KA.Regulation of gastric carcinogenesis by inflammatory cytokines.Cell Mol Gastroenter Hepatol2017;4:47-53 PMCID:PMC5439239

[154] Qian S,Zhan X.Chronic inflammation: key player and biomarker-set to predict and prevent cancer development and progression based on individualized patient profiles.EPMA J2019;10:365-81 PMCID:PMC6882964

[155] He S,Liu X.Advances and challenges in the treatment of esophageal cancer.Acta Pharm Sin B2021;11:3379-92 PMCID:PMC8642427

[156] Ashrafi A,Modareszadeh P.Current landscape of therapeutic resistance in lung cancer and promising strategies to overcome resistance.Cancers2022;14:4562 PMCID:PMC9558974

[157] Marin JJ,Lozano E.Mechanisms of resistance to chemotherapy in gastric cancer.Anti Agent Med Chem2016;16:318-34

[158] Wang Q,Chen G.Drug resistance in colorectal cancer: from mechanism to clinic.Cancers2022;14:2928 PMCID:PMC9221177

[159] Scott AK,Neu CP.Mechanically induced alterations in chromatin architecture guide the balance between cell plasticity and mechanical memory.Front Cell Dev Biol2023;11:1084759 PMCID:PMC10151697

[160] Burnet FM.The Concept of immunological surveillance.Prog Exp Tumor Res1970;13:1-27

[161] Dunn GP,Ikeda H,Schreiber RD.Cancer immunoediting: from immunosurveillance to tumor escape.Nat Immunol2002;3:991-8

[162] Penn I.Posttransplant malignancies.Transplant Proc1999;31:1260-2

[163] Sheil AG.Cancer after transplantation.World J Surg1986;10:389-96

[164] Penn I.Malignant melanoma in organ allograft recipients.Transplantation1996;61:274-8

[165] Penn I.Sarcomas in organ allograft recipients.Transplantation1995;60:1485-91

[166] Pham SM,Landreneau RJ.Solid tumors after heart transplantation: lethality of lung cancer.Ann Thorac Surg1995;60:1623-6

[167] Nair SS,Dovey Z,Tewari AK.The tumor microenvironment and immunotherapy in prostate and bladder cancer.Urol Clin North Am2020;47:e17-54

[168] Zhong C,Yang J.Immunotherapy for hepatocellular carcinoma: current limits and prospects.Front Oncol2021;11:589680 PMCID:PMC8039369

[169] Jia D,Kwon OJ.Stromal FOXF2 suppresses prostate cancer progression and metastasis by enhancing antitumor immunity.Nat Commun2022;13:6828 PMCID:PMC9652358

[170] Lander VE,Kingston NL.Stromal reprogramming by FAK inhibition overcomes radiation resistance to allow for immune priming and response to checkpoint blockade.Cancer Discov2022;12:2774-99

[171] Yang D,Yuan QE.Suppressive stroma-immune prognostic signature impedes immunotherapy in ovarian cancer and can be reversed by PDGFRB inhibitors.J Transl Med2023;21:586 PMCID:PMC10472577

[172] Bremnes RM,Al-Saad S.The role of tumor stroma in cancer progression and prognosis: emphasis on carcinoma-associated fibroblasts and non-small cell lung cancer.J Thorac Oncol2011;6:209-17

[173] Nishikawa H.Mechanisms of regulatory T cell infiltration in tumors: implications for innovative immune precision therapies.J Immunother Cancer2021;9:e002591 PMCID:PMC8327843

[174] Lunardi S,Lim SY.IP-10/CXCL10 induction in human pancreatic cancer stroma influences lymphocytes recruitment and correlates with poor survival.Oncotarget2014;5:11064-80 PMCID:PMC4294325

[175] Vilgelm AE.Chemokines modulate immune surveillance in tumorigenesis, metastasis, and response to immunotherapy.Front Immunol2019;10:333 PMCID:PMC6400988

[176] Hussain S,Cherian M,Ahirwar DK.The roles of stroma-derived chemokine in different stages of cancer metastases.Front Immunol2020;11:598532 PMCID:PMC7783453

[177] Deng J,Meng E.CXCL5: a coachman to drive cancer progression.Front Oncol2022;12:944494 PMCID:PMC9376318

[178] Kraman M,Arnold JN.Suppression of antitumor immunity by stromal cells expressing fibroblast activation protein-alpha.Science2010;330:827-30

[179] Poznansky MC,Foxall R,Luster AD.Active movement of T cells away from a chemokine.Nat Med2000;6:543-8

[180] Kryczek I,Keller E,Zou W.Stroma-derived factor (SDF-1/CXCL12) and human tumor pathogenesis.Am J Physiol Cell Physiol2007;292:C987-95

[181] Schreiber H.Cancer. Awakening immunity.Science2010;330:761-2

[182] Yang L,Moses HL.TGF-beta and immune cells: an important regulatory axis in the tumor microenvironment and progression.Trends Immunol2010;31:220-7 PMCID:PMC2891151

[183] Shi X,Zhou H.Transforming growth factor-β signaling in fibrotic diseases and cancer-associated fibroblasts.Biomolecules2020;10:1666 PMCID:PMC7763058

[184] Mariathasan S,Nickles D.TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells.Nature2018;554:544-8

[185] Zippi M,Minervini G.Desmoplasia influenced recurrence of disease and mortality in stage III colorectal cancer within five years after surgery and adjuvant therapy.Saudi J Gastroenterol2017;23:39-44 PMCID:PMC5329976

[186] Whatcott CJ,Von Hoff DD. Chapter 8 desmoplasia and chemoresistance in pancreatic cancer. In: Grippo PJ, Munshi HG, editors. Pancreatic cancer and tumor microenvironment. India: Trivandrum; 2012. Available from: https://www.ncbi.nlm.nih.gov/books/NBK98939/ [Last accessed on 22 Jul 2024]

[187] DeClerck YA.Desmoplasia: a response or a niche?.Cancer Discov2012;2:772-4

[188] González-González L.Periostin: a matricellular protein with multiple functions in cancer development and progression.Front Oncol2018;8:225 PMCID:PMC6005831

[189] Wei T,Liu S.Periostin deficiency reduces PD-1⁺ tumor-associated macrophage infiltration and enhances anti-PD-1 efficacy in colorectal cancer.Cell Rep2023;42:112090

[190] Mortezaee K.Immune escape: a critical hallmark in solid tumors.Life Sci2020;258:118110

[191] Galon J.Approaches to treat immune hot, altered and cold tumours with combination immunotherapies.Nat Rev Drug Discov2019;18:197-218

[192] Hussein MR,Musalam AO.Phenotypic characterization of the infiltrating immune cells in normal prostate, benign nodular prostatic hyperplasia and prostatic adenocarcinoma.Exp Mol Pathol2009;86:108-13

[193] von Amsberg G,Karagiannis P.Immunotherapy in advanced prostate cancer-light at the end of the tunnel?.Int J Mol Sci2022;23:2569 PMCID:PMC8910587

[194] Anker JF,Mok H,Abdulkadir SA.Multi-faceted immunomodulatory and tissue-tropic clinical bacterial isolate potentiates prostate cancer immunotherapy.Nat Commun2018;9:1591 PMCID:PMC5913311

[195] Vareki S. High and low mutational burden tumors versus immunologically hot and cold tumors and response to immune checkpoint inhibitors.J Immunother Cancer2018;6:157 PMCID:PMC6307306

[196] Wang I,Wang BY,Uchio E.Prostate cancer immunotherapy: a review of recent advancements with novel treatment methods and efficacy.Am J Clin Exp Urol2022;10:210-33 PMCID:PMC9428569

[197] Ma Z,Dong B.Docetaxel remodels prostate cancer immune microenvironment and enhances checkpoint inhibitor-based immunotherapy.Theranostics2022;12:4965-79 PMCID:PMC9274752

[198] Chesner L,Polesso F.Abstract B041: AR suppresses MHC class I expression and T-cell response in prostate cancer.Cancer Res2023;83:B041

[199] Kogan-Sakin I,Paland N.Prostate stromal cells produce CXCL-1, CXCL-2, CXCL-3 and IL-8 in response to epithelia-secreted IL-1.Carcinogenesis2009;30:698-705

[200] Tse BW,Russell PJ.Paradoxical roles of tumour necrosis factor-alpha in prostate cancer biology.Prostate Cancer2012;2012:128965 PMCID:PMC3543804

[201] Smith BN,Billet S.Antagonizing CD105 and androgen receptor to target stromal-epithelial interactions for clinical benefit.Mol Ther2023;31:78-89 PMCID:PMC9840108

[202] Zhou C,Ding P,Ji G.The role of CXCL family members in different diseases.Cell Death Discov2023;9:212 PMCID:PMC10314943

[203] Bullock K.Suppressing MDSC recruitment to the tumor microenvironment by antagonizing CXCR2 to enhance the efficacy of immunotherapy.Cancers2021;13:6293 PMCID:PMC8699249

[204] Korbecki J,Chlubek M,Gutowska I.CXCR2 receptor: regulation of expression, signal transduction, and involvement in cancer.Int J Mol Sci2022;23:2168 PMCID:PMC8878198

[205] Di Mitri D,Vasilevska J.Re-education of tumor-associated macrophages by CXCR2 blockade drives senescence and tumor inhibition in advanced prostate cancer.Cell Rep2019;28:2156-2168.e5 PMCID:PMC6715643

[206] Bahig H,Delouya G.Neutrophil count is associated with survival in localized prostate cancer.BMC Cancer2015;15:594 PMCID:PMC4546219

[207] Sharma J,Harshman LC.Elevated IL-8, TNF-α, and MCP-1 in men with metastatic prostate cancer starting androgen-deprivation therapy (ADT) are associated with shorter time to castration-resistance and overall survival.Prostate2014;74:820-8

[208] Minas TZ,Dorsey TH.Serum proteomics links suppression of tumor immunity to ancestry and lethal prostate cancer.Nat Commun2022;13:1759 PMCID:PMC8975871

[209] Wallace TA,Yi M.Tumor immunobiological differences in prostate cancer between African-American and European-American men.Cancer Res2008;68:927-36

[210] Zhu W,Huang J.Multi-omics analysis reveals a macrophage-related marker gene signature for prognostic prediction, immune landscape, genomic heterogeneity, and drug choices in prostate cancer.Front Immunol2023;14:1122670 PMCID:PMC10140525

[211] Chen C,Wang X.Identification of prostate cancer subtypes based on immune signature scores in bulk and single-cell transcriptomes.Med Oncol2022;39:123

[212] Guo T,Yan S.A combined signature of glycolysis and immune landscape predicts prognosis and therapeutic response in prostate cancer.Front Endocrinol2022;13:1037099 PMCID:PMC9634133

[213] Ren C,Wang S.Metabolic syndrome-related prognostic index: predicting biochemical recurrence and differentiating between cold and hot tumors in prostate cancer.Front Endocrinol2023;14:1148117 PMCID:PMC10080042

[214] Li N,Lin Z.Development of a novel immune subtyping system expanded with immune landscape and an 11-gene signature for predicting prostate cancer survival.J Oncol2022;2022:1183173 PMCID:PMC8866019

[215] Keam SP,Nguyen T.High dose-rate brachytherapy of localized prostate cancer converts tumors from cold to hot.J Immunother Cancer2020;8:e000792 PMCID:PMC7319782

[216] Shen Y,Long M.Screening to identify an immune landscape-based prognostic predictor and therapeutic target for prostate cancer.Front Oncol2021;11:761643 PMCID:PMC8602809

[217] Zhang G.An immune-related lncRNA signature to predict the biochemical recurrence and immune landscape in prostate cancer.Int J Gen Med2021;14:9031-49 PMCID:PMC8643172

[218] Hanahan D.Hallmarks of cancer: the next generation.Cell2011;144:646-74

[219] Antognelli C,Prosperi E,Talesa VN.Glyoxalase-1-dependent methylglyoxal depletion sustains PD-L1 expression in metastatic prostate cancer cells: a novel mechanism in cancer immunosurveillance escape and a potential novel target to overcome PD-L1 blockade resistance.Cancers2021;13:2965 PMCID:PMC8232032

[220] Datta M,Nishikawa H,Jain RK.Reprogramming the tumor microenvironment to improve immunotherapy: emerging strategies and combination therapies.Am Soc Clin Oncol Educ Book2019;39:165-74 PMCID:PMC6596289

[221] Perera MPJ,Risbridger GP.Chimeric antigen receptor T-cell therapy in metastatic castrate-resistant prostate cancer.Cancers2022;14:503 PMCID:PMC8833489

[222] Bander NH,Milowsky MI,Vallabahajosula S.Targeted systemic therapy of prostate cancer with a monoclonal antibody to prostate-specific membrane antigen.Semin Oncol2003;30:667-76

[223] Sardinha M,Barreira JV,Pacey S.Antibody-drug conjugates in prostate cancer: a systematic review.Cureus2023;15:e34490 PMCID:PMC9983052

[224] Kamat NV,Lee JK.BiTE-ing into prostate cancer with bispecific T-cell engagers.Clin Cancer Res2021;27:2675-7 PMCID:PMC8127346

[225] Yang K,Luo Z.Oncolytic adenovirus, a new treatment strategy for prostate cancer.Biomedicines2022;10:3262 PMCID:PMC9775875

[226] Pieczonka CM,Mouraviev V.Sipuleucel-T for the treatment of patients with metastatic castrate-resistant prostate cancer: considerations for clinical practice.Rev Urol2015;17:203-10 PMCID:PMC4735666

[227] Kantoff PW,Shore ND.Sipuleucel-T immunotherapy for castration-resistant prostate cancer.N Engl J Med2010;363:411-22

[228] Donninger H,Eaton JW.Cancer vaccines: promising therapeutics or an unattainable dream.Vaccines2021;9:668 PMCID:PMC8233841

[229] Chen S,Wu JD.CD73: an emerging checkpoint for cancer immunotherapy.Immunotherapy2019;11:983-97 PMCID:PMC6609898

[230] Mbongue JC,Torrez TW,Firek AF.The role of indoleamine 2, 3-dioxygenase in immune suppression and autoimmunity.Vaccines2015;3:703-29 PMCID:PMC4586474

[231] Solinas C,De Silva P.LAG3: the biological processes that motivate targeting this immune checkpoint molecule in human cancer.Cancers2019;11:1213 PMCID:PMC6721578

[232] Miller RA,Hu S.Anti-CD73 antibody activates human B cells, enhances humoral responses and induces redistribution of B cells in patients with cancer.J Immunother Cancer2022;10:e005802 PMCID:PMC9723961

[233] Fan X,Sepulveda MA,Allison JP.Engagement of the ICOS pathway markedly enhances efficacy of CTLA-4 blockade in cancer immunotherapy.J Exp Med2014;211:715-25 PMCID:PMC3978270

[234] Fu Y,Zhang Z.Therapeutic strategies for the costimulatory molecule OX40 in T-cell-mediated immunity.Acta Pharm Sin B2020;10:414-33 PMCID:PMC7049610

[235] Ye L,Wang L.CD137, an attractive candidate for the immunotherapy of lung cancer.Cancer Sci2020;111:1461-7 PMCID:PMC7226203

[236] Bayer AL,Malek TR.The IL-2/IL-2R system: from basic science to therapeutic applications to enhance immune regulation.Immunol Res2013;57:197-209 PMCID:PMC3990437

[237] Schepisi G,Casadei C.CAR-T cell therapy: a potential new strategy against prostate cancer.J Immunother Cancer2019;7:258 PMCID:PMC6794851

[238] Patel S,Powell AB.Beyond CAR T cells: other cell-based immunotherapeutic strategies against cancer.front oncol2019;9:196 PMCID:PMC6467966

[239] Mills JK,Giuffrida L.Generating CAR T cells from tumor-infiltrating lymphocytes.Ther Adv Vaccines Immunother2021;9:25151355211017119 PMCID:PMC8186112

[240] Zhou B,Long Y.Notch signaling pathway: architecture, disease, and therapeutics.Signal Transduct Target Ther2022;7:95 PMCID:PMC8948217

[241] Day KC,Kozminsky M.HER2 and EGFR overexpression support metastatic progression of prostate cancer to bone.Cancer Res2017;77:74-85 PMCID:PMC5214538

[242] Hsu EC,Bermudez A.Trop2 is a driver of metastatic prostate cancer with neuroendocrine phenotype via PARP1.Proc Natl Acad Sci USA2020;117:2032-42 PMCID:PMC6994991

[243] Rosellini M,Mollica V.Treating prostate cancer by antibody-drug conjugates.Int J Mol Sci2021;22:1551 PMCID:PMC7913806

[244] Tian Z,Zhang Y.Bispecific T cell engagers: an emerging therapy for management of hematologic malignancies.J Hematol Oncol2021;14:75 PMCID:PMC8091790

[245] Lin D,Liang T.Oncolytic virotherapy: basic principles, recent advances and future directions.Signal Transduct Target Ther2023;8:156 PMCID:PMC10090134

[246] Lee J,Nair S,Gilboa E.Tumor immunotherapy targeting fibroblast activation protein, a product expressed in tumor-associated fibroblasts.Cancer Res2005;65:11156-63

[247] Wen Y,Ma TT.Immunotherapy targeting fibroblast activation protein inhibits tumor growth and increases survival in a murine colon cancer model.Cancer Sci2010;101:2325-32 PMCID:PMC11158467

[248] Yu F,Guo ZS,Gottschalk SM.T-cell engager-armed oncolytic vaccinia virus significantly enhances antitumor therapy.Mol Ther2014;22:102-11 PMCID:PMC3978793

[249] Freedman JD,Lei-Rossmann J.An oncolytic virus expressing a T-cell engager simultaneously targets cancer and immunosuppressive stromal cells.Cancer Res2018;78:6852-65

[250] Chaudary N,Jelveh S,Hill RP.Plerixafor improves primary tumor response and reduces metastases in cervical cancer treated with radio-chemotherapy.Clin Cancer Res2017;23:1242-9

[251] Kim ST,Park SH.First-in-human phase I trial of anti-hepatocyte growth factor antibody (YYB101) in refractory solid tumor patients.Ther Adv Med Oncol2020;12:1758835920926796 PMCID:PMC7268171

[252] Zhang X.Effects of thalidomide on growth and VEGF-A expression in SW480 colon cancer cells.Oncol Lett2018;15:3313-20 PMCID:PMC5778822

[253] Pulte ED,Nie L.FDA approval summary: lenalidomide as maintenance therapy after autologous stem cell transplant in newly diagnosed multiple myeloma.Oncologist2018;23:734-9 PMCID:PMC6067941

[254] Summers J,Keegan P.FDA drug approval summary: bevacizumab plus interferon for advanced renal cell carcinoma.Oncologist2010;15:104-11 PMCID:PMC3227879

[255] Singh AD.Ramucirumab (Cyramza): a breakthrough treatment for gastric cancer.P T2015;40:430-68. PMCID:PMC4495869

[256] Chiorean EG,Youssoufian H.A phase I study of olaratumab, an anti-platelet-derived growth factor receptor alpha (PDGFRα) monoclonal antibody, in patients with advanced solid tumors.Cancer Chemother Pharmacol2014;73:595-604

[257] Kwon MJ.Matrix metalloproteinases as therapeutic targets in breast cancer.Front Oncol2022;12:1108695 PMCID:PMC9897057

[258] Nadal L,Villa A.Novel human monoclonal antibodies specific to the alternatively spliced domain D of Tenascin C efficiently target tumors in vivo.MAbs2020;12:1836713 PMCID:PMC7646483

[259] Neesse A,Bapiro TE.CTGF antagonism with mAb FG-3019 enhances chemotherapy response without increasing drug delivery in murine ductal pancreas cancer.Proc Natl Acad Sci USA2013;110:12325-30 PMCID:PMC3725120

[260] Ke FY,Lin MC,Kuo KT.Novel monoclonal antibody against integrin α3 shows therapeutic potential for ovarian cancer.Cancer Sci2020;111:3478-92 PMCID:PMC7541015

[261] Sun Y,Ye Y.High expression of fibronectin 1 indicates poor prognosis in gastric cancer.Oncol Lett2020;19:93-102 PMCID:PMC6923922

[262] Streel G, Lucas S. Targeting immunosuppression by TGF-β1 for cancer immunotherapy.Biochem Pharmacol2021;192:114697 PMCID:PMC8484859

[263] Ma C,Sun H,Pei Y.Identifying the oncogenic roles of FAP in human cancers based on systematic analysis.Aging2023;15:7056-83 PMCID:PMC10415543

[264] Martori C,Paul T.Macrophages as a therapeutic target in metastatic prostate cancer: a way to overcome immunotherapy resistance?.Cancers2022;14:440 PMCID:PMC8773572

[265] Gordon S.The mononuclear phagocytic system. generation of diversity.Front Immunol2019;10:1893 PMCID:PMC6696592

[266] Martinez FO.The M1 and M2 paradigm of macrophage activation: time for reassessment.F1000Prime Rep2014;6:13 PMCID:PMC3944738

[267] Das A,Datta S.Monocyte and macrophage plasticity in tissue repair and regeneration.Am J Pathol2015;185:2596-606 PMCID:PMC4607753

[268] Gordon S.Tissue macrophages: heterogeneity and functions.BMC Biol2017;15:53 PMCID:PMC5492929

[269] He MX,Crowdis J.Transcriptional mediators of treatment resistance in lethal prostate cancer.Nat Med2021;27:426-33 PMCID:PMC7960507

[270] Stout RD,Matta B,Watkins SK.Macrophages sequentially change their functional phenotype in response to changes in microenvironmental influences.J Immunol2005;175:342-9

[271] Li XF,Zhou HL.Macrophages promote anti-androgen resistance in prostate cancer bone disease.J Exp Med2023;220 PMCID:PMC9948761

[272] Mantovani A,Marchesi F.Macrophages as tools and targets in cancer therapy.Nat Rev Drug Discov2022;21:799-820 PMCID:PMC9380983

[273] Abram CL.The diverse functions of Src family kinases in macrophages.Front Biosci2008;13:4426-50 PMCID:PMC4457449

[274] Loi M,Sottili M.Tumor-associated macrophages (TAMs) modulate response to HER2-targeted agents in a humanized mouse model of breast cancer.Clin Transl Oncol2022;24:1395-402

[275] Watanabe H,Nishii K.A long-term response to nivolumab in a case of PD-L1-negative lung adenocarcinoma with an EGFR mutation and surrounding PD-L1-positive tumor-associated macrophages.Intern Med2019;58:3033-7 PMCID:PMC6859382

[276] Su S,Wang X.Induced CAR-macrophages as a novel therapeutic cell type for cancer immune cell therapies.Cells2022;11:1652 PMCID:PMC9139529

[277] Liu M,Liang Z.CAR-macrophages and CAR-T cells synergistically kill tumor cells in vitro.Cells2022;11:3692 PMCID:PMC9688246

[278] Huber ML,Parker C.Interdisciplinary critique of sipuleucel-T as immunotherapy in castration-resistant prostate cancer.J Natl Cancer Inst2012;104:273-9 PMCID:PMC3283534

[279] Murphy G,Ragde H,Boynton A.Phase I clinical trial: T-cell therapy for prostate cancer using autologous dendritic cells pulsed with HLA-A0201-specific peptides from prostate-specific membrane antigen.Prostate1996;29:371-80

[280] Tjoa B,Bowes V.Follow-up evaluation of prostate cancer patients infused with autologous dendritic cells pulsed with PSMA peptides.Prostate1997;32:272-8

[281] Jähnisch H,Kiessling A.Dendritic cell-based immunotherapy for prostate cancer.Clin Dev Immunol2010;2010:517493 PMCID:PMC2975068

[282] Kiessling A,Füssel S,Wirth MP.Tumor-associated antigens for specific immunotherapy of prostate cancer.Cancers2012;4:193-217 PMCID:PMC3712678

[283] Kitamura H,Asanuma H,Sato N.Down-regulation of HLA class I antigens in prostate cancer tissues and up-regulation by histone deacetylase inhibition.J Urol2007;178:692-6

[284] Lozano M,Benitez-Ribas D.Technical challenges in the manufacture of dendritic cell cancer therapies.Eur Oncol Haematol2019;15:22-8

[285] Kongsted P,Ellebaek E.Dendritic cell vaccination in combination with docetaxel for patients with metastatic castration-resistant prostate cancer: a randomized phase II study.Cytotherapy2017;19:500-13

[286] Glabman RA,Sato N.Cancer-associated fibroblasts: tumorigenicity and targeting for cancer therapy.Cancers2022;14:3906 PMCID:PMC9405783

[287] Boudewijns S,Koornstra RH.Immune-related adverse events of dendritic cell vaccination correlate with immunologic and clinical outcome in stage III and IV melanoma patients.J Immunother2016;39:241-8 PMCID:PMC4902323

[288] Agrawal A,Prakash S.Dendritic cells and aging: consequences for autoimmunity.Expert Rev Clin Immunol2012;8:73-80 PMCID:PMC3285507