The interaction of innate immune and adaptive immune system

Abstract

The innate immune system serves as the body’s first line of defense, utilizing pattern recognition receptors like Toll-like receptors to detect pathogens and initiate rapid response mechanisms. Following this initial response, adaptive immunity provides highly specific and sustained killing of pathogens via B cells, T cells, and antibodies. Traditionally, it has been assumed that innate immunity activates adaptive immunity; however, recent studies have revealed more complex interactions. This review provides a detailed dissection of the composition and function of the innate and adaptive immune systems, emphasizing their synergistic roles in physiological and pathological contexts, providing new insights into the link between these two forms of immunity. Precise regulation of both immune systems at the same time is more beneficial in the fight against immune-related diseases, for example, the cGAS–STING pathway has been found to play an important role in infections and cancers. In addition, this paper summarizes the challenges and future directions in the field of immunity, including the latest single-cell sequencing technologies, CAR-T cell therapy, and immune checkpoint inhibitors. By summarizing these developments, this review aims to enhance our understanding of the complexity interactions between innate and adaptive immunity and provides new perspectives in understanding the immune system.

Keywords

adaptive immunity / disease pathogenesis / immunotherapy / innate immunity

References

[1] Carpenter S, O’Neill LAJ. From periphery to center stage: 50 years of advancements in innate immunity. Cell. 2024; 187(9): 2030-2051.

[2] Janeway CA. Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harb Symp Quant Biol. 1989; 54 Pt 1: 1-13.

[3] Dai J, Fang P, Saredy J, et al. Metabolism-associated danger signal-induced immune response and reverse immune checkpoint-activated CD40+ monocyte differentiation. J Hematol Oncol. 2017; 10: 141.

[4] Jain A, Pasare C. Innate control of adaptive immunity: beyond the three-signal paradigm. J Immunol. 2017; 198(10): 3791-3800.

[5] Iwasaki A, Medzhitov R. Control of adaptive immunity by the innate immune system. Nat Immunol. 2015; 16(4): 343-353.

[6] Palm NW, Rosenstein RK, Medzhitov R. Allergic host defences. Nature. 2012; 484(7395): 465-472.

[7] Warner JD, Irizarry-Caro RA, Bennion BG, et al. STING-associated vasculopathy develops independently of IRF3 in mice. J Exp Med. 2017; 214(11): 3279-3292.

[8] Luksch H, Stinson WA, Platt DJ, et al. STING-associated lung disease in mice relies on T cells but not type I interferon. J Allergy Clin Immunol. 2019; 144(1): 254-266.e8.

[9] Lee HJ, Kim M. Skin barrier function and the microbiome. Int J Mol Sci. 2022; 23(21): 13071.

[10] Gallo RL, Hooper LV. Epithelial antimicrobial defence of the skin and intestine. Nat Rev Immunol. 2012; 12(7): 503-516.

[11] Kalló G, Kumar A, Tőzsér J, Csősz É. Chemical barrier proteins in human body fluids. Biomedicines. 2022; 10(7): 1472.

[12] Alemao CA, Budden KF, Gomez HM, et al. Impact of diet and the bacterial microbiome on the mucous barrier and immune disorders. Allergy. 2021; 76(3): 714-734.

[13] Wertz PW, De Szalay S. Innate antimicrobial defense of skin and oral mucosa. Antibiotics. 2020; 9(4): 159.

[14] Murphy K, Weaver C. Janeway’s Lmmunobiology. 9th ed. Garland Science; 2017.

[15] Thaiss CA, Zmora N, Levy M, Elinav E. The microbiome and innate immunity. Nature. 2016; 535(7610): 65-74.

[16] Vandenabeele S, Wu L. Dendritic cell origins: puzzles and paradoxes. Immunol Cell Biol. 1999; 77(5): 411-419.

[17] Wu L, Liu YJ. Development of dendritic-cell lineages. Immunity. 2007; 26(6): 741-750.

[18] Merad M, Sathe P, Helft J, Miller J, Mortha A. The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu Rev Immunol. 2013; 31: 563-604.

[19] Modrow S, Falke D, Truyen U, Schätzl H. Immunology. In: Molecular Virology. Springer; 2013: 69-94.

[20] Borregaard N. Neutrophils, from marrow to microbes. Immunity. 2010; 33(5): 657-670.

[21] Klion AD, Nutman TB. The role of eosinophils in host defense against helminth parasites. J Allergy Clin Immunol. 2004; 113(1): 30-37.

[22] Miyake K, Karasuyama H. Emerging roles of basophils in allergic inflammation. Allergol Int. 2017; 66(3): 382-391.

[23] Mukai K, Tsai M, Saito H, Galli SJ. Mast cells as sources of cytokines, chemokines, and growth factors. Immunol Rev. 2018; 282(1): 121-150.

[24] Stone KD, Prussin C, Metcalfe DD. IgE, mast cells, basophils, and eosinophils. J Allergy Clin Immunol. 2010; 125(2 Suppl 2): S73-80.

[25] Fiebiger E, Bischoff SC. Mucosal basophils, eosinophils, and mast cells. In: Principles of Mucosal Immunology. 2nd ed. Garland Science; 2020.

[26] Lavin Y, Mortha A, Rahman A, Merad M. Regulation of macrophage development and function in peripheral tissues. Nat Rev Immunol. 2015; 15(12): 731-744.

[27] Chaintreuil P, Kerreneur E, Bourgoin M, et al. The generation, activation, and polarization of monocyte-derived macrophages in human malignancies. Front Immunol. 2023; 14: 1178337.

[28] Caligiuri MA. Human natural killer cells. Blood. 2008; 112(3): 461-469.

[29] Lanier LL. NK cell recognition. Annu Rev Immunol. 2005; 23: 225-274.

[30] Bendelac A, Savage PB, Teyton L. The biology of NKT cells. Annu Rev Immunol. 2007; 25(1): 297-336.

[31] Courtney AN, Tian G, Metelitsa LS. Natural killer T cells and other innate-like T lymphocytes as emerging platforms for allogeneic cancer cell therapy. Blood. 2023; 141(8): 869-876.

[32] Godfrey DI, Stankovic S, Baxter AG. Raising the NKT cell family. Nat Immunol. 2010; 11(3): 197-206.

[33] Sciammas R, Tatsumi Y, Sperling AI, Arunan K, Bluestone JA. TCR gamma delta cells: mysterious cells of the immune system. Immunol Res. 1994; 13(4): 268-279.

[34] Pistoia V, Tumino N, Vacca P, et al. Human γδ T-cells: from surface receptors to the therapy of high-risk leukemias. Front Immunol. 2018; 9: 984.

[35] Saura-Esteller J, de Jong M, King LA, et al. Gamma Delta T-cell based cancer immunotherapy: past-present-future. Front Immunol. 2022; 13: 915837.

[36] Pieper K, Grimbacher B, Eibel H. B-cell biology and development. J Allergy Clin Immunol. 2013; 131(4): 959-971.

[37] Montecino-Rodriguez E, Dorshkind K. B-1 B cell development in the fetus and adult. Immunity. 2012; 36(1): 13-21.

[38] Morris G, Puri BK, Olive L, Carvalho AF, Berk M, Maes M. Emerging role of innate B1 cells in the pathophysiology of autoimmune and neuroimmune diseases: association with inflammation, oxidative and nitrosative stress and autoimmune responses. Pharmacol Res. 2019; 148: 104408.

[39] Prieto JMB, Felippe MJB. Development, phenotype, and function of non-conventional B cells. Comp Immunol Microbiol Infect Dis. 2017; 54: 38-44.

[40] She Z, Li C, Wu F, et al. The role of B1 cells in systemic lupus erythematosus. Front Immunol. 2022; 13: 814857.

[41] Marinkovic D, Marinkovic T. Putative role of marginal zone B cells in pathophysiological processes. Scand J Immunol. 2020; 92(3): e12920.

[42] Spits H, Artis D, Colonna M, et al. Innate lymphoid cells — a proposal for uniform nomenclature. Nat Rev Immunol. 2013; 13(2): 145-149.

[43] Vivier E, Artis D, Colonna M, et al. Innate lymphoid cells: 10 years on. Cell. 2018; 174(5): 1054-1066.

[44] Eberl G, Di Santo JP, Vivier E. The brave new world of innate lymphoid cells. Nat Immunol. 2015; 16(1): 1-5.

[45] Kemper C, Ferreira VP, Paz JT, Holers MV, Lionakis MS, Alexander JJ. Complement: the road less travelled. J Immunol. 2023; 210(2): 119-125.

[46] Trouw LA, Daha MR. Role of complement in innate immunity and host defense. Immunol Lett. 2011; 138(1): 35-37.

[47] Noris M, Remuzzi G. Overview of complement activation and regulation. Semin Nephrol. 2013; 33(6): 479-492.

[48] West EE, Kemper C. Complosome — the intracellular complement system. Nat Rev Nephrol. 2023; 19(7): 426-439. Published online April 13, 2023:1-14.

[49] Afshar-Kharghan V. The role of the complement system in cancer. J Clin Invest. 2017; 127(3): 780-789.

[50] Botto M. Links between complement deficiency and apoptosis. Arthritis Res. 2001; 3(4): 207-210.

[51] Commins SP, Borish L, Steinke JW. Immunologic messenger molecules: cytokines, interferons, and chemokines. J Allergy Clin Immunol. 2010; 125(2 Suppl 2): S53-72.

[52] Murphy K, Weaver C. Janeway’s Immunobiology. Garland Science; 2016.

[53] Ma M, Jiang W, Zhou R. DAMPs and DAMP-sensing receptors in inflammation and diseases. Immunity. 2024; 57(4): 752-771.

[54] Janeway CA, Medzhitov R. Innate immune recognition. Annu Rev Immunol. 2002; 20: 197-216.

[55] Song W, Wang J, Han Z, et al. Structural basis for specific recognition of single-stranded RNA by Toll-like receptor 13. Nat Struct Mol Biol. 2015; 22(10): 782-787.

[56] Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol. 2010; 11(5): 373-384.

[57] Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006; 124(4): 783-801.

[58] Davis BK, Wen H, Ting JPY. The inflammasome NLRs in immunity, inflammation, and associated diseases. Annu Rev Immunol. 2011; 29: 707-735.

[59] Linde A, Wachter B, Höner OP, et al. Natural history of innate host defense peptides. Probiotics Antimicrob Proteins. 2009; 1(2): 97-112.

[60] Fiuza C, Suffredini AF. Human models of innate immunity: local and systemic inflammatory responses. J Endotoxin Res. 2001;7(5):385-8.

[61] Abdulkhaleq LA, Assi MA, Abdullah R, Zamri-Saad M, Taufiq-Yap YH, Hezmee MNM. The crucial roles of inflammatory mediators in inflammation: a review. Vet World. 2018; 11(5): 627-635.

[62] Gleeson M, Bishop NC, Stensel DJ, Lindley MR, Mastana SS, Nimmo MA. The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. Nat Rev Immunol. 2011; 11(9): 607-615.

[63] Netea MG, Domínguez-Andrés J, Barreiro LB, et al. Defining trained immunity and its role in health and disease. Nat Rev Immunol. 2020; 20(6): 375-388.

[64] Crişan TO, Netea MG, Joosten LAB. Innate immune memory: implications for host responses to damage-associated molecular patterns. Eur J Immunol. 2016; 46(4): 817-828.

[65] Jiang Z, Zhu H, Wang P, et al. Different subpopulations of regulatory T cells in human autoimmune disease, transplantation, and tumor immunity. MedComm. 2022; 3(2): e137.

[66] Ma H, O’Kennedy R. The structure of natural and recombinant antibodies. Methods Mol Biol. 2015; 1348: 7-11.

[67] Benvenuti F. The dendritic cell synapse: a life dedicated to T cell activation. Front Immunol. 2016; 7: 70.

[68] Nikolich-Zugich J, Slifka MK, Messaoudi I. The many important facets of T-cell repertoire diversity. Nat Rev Immunol. 2004; 4(2): 123-132.

[69] Rudolph MG, Stanfield RL, Wilson IA. How TCRs bind MHCs, peptides, and coreceptors. Annu Rev Immunol. 2006; 24: 419-466.

[70] Nutt SL, Hodgkin PD, Tarlinton DM, Corcoran LM. The generation of antibody-secreting plasma cells. Nat Rev Immunol. 2015; 15(3): 160-171.

[71] Lam N, Lee Y, Farber DL. A guide to adaptive immune memory. Nat Rev Immunol. Published online June 3, 2024.

[72] Li P, Zhang Y, Xu Y, Cao H, Li L. Characteristics of CD8+ and CD4+ tissue-resident memory lymphocytes in the gastrointestinal tract. Adv Gut Microbiome Res. 2022; 2022(1): 9157455.

[73] Inoue T, Kurosaki T. Memory B cells. Nat Rev Immunol. 2024; 24(1): 5-17.

[74] Cancro MP, Tomayko MM. Memory B cells and plasma cells: the differentiative continuum of humoral immunity. Immunol Rev. 2021; 303(1): 72-82.

[75] Geissmann F, Manz MG, Jung S, Sieweke MH, Merad M, Ley K. Development of monocytes, macrophages, and dendritic cells. Science. 2010; 327(5966): 656-661.

[76] Briseño CG, Murphy TL, Murphy KM. Complementary diversification of dendritic cells and innate lymphoid cells. Curr Opin Immunol. 2014; 29: 69-78.

[77] Satpathy AT, Wu X, Albring JC, Murphy KM. Re(de)fining the dendritic cell lineage. Nat Immunol. 2012; 13(12): 1145-1154.

[78] Lanier LL. Up on the tightrope: natural killer cell activation and inhibition. Nat Immunol. 2008; 9(5): 495-502.

[79] Galli SJ, Tsai M, Piliponsky AM. The development of allergic inflammation. Nature. 2008; 454(7203): 445-454.

[80] Wynn TA, Vannella KM. Macrophages in tissue repair, regeneration, and fibrosis. Immunity. 2016; 44(3): 450-462.

[81] Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 cells. Annu Rev Immunol. 2009; 27(1): 485-517.

[82] Edelson BT, Bradstreet TR, Kc W, et al. Batf3-dependent CD11b(low/-) peripheral dendritic cells are GM-CSF-independent and are not required for Th cell priming after subcutaneous immunization. PLoS One. 2011; 6(10): e25660.

[83] Mashayekhi M, Sandau MM, Dunay IR, et al. CD8α(+) dendritic cells are the critical source of interleukin-12 that controls acute infection by Toxoplasma gondii tachyzoites. Immunity. 2011; 35(2): 249-259.

[84] Zhu J, Yamane H, Paul WE. Differentiation of effector CD4 T cell populations (*). Annu Rev Immunol. 2010; 28: 445-489.

[85] Kaiko GE, Horvat JC, Beagley KW, Hansbro PM. Immunological decision-making: how does the immune system decide to mount a helper T-cell response? Immunology. 2008; 123(3): 326-338.

[86] Soudja SM, Chandrabos C, Yakob E, Veenstra M, Palliser D, Lauvau G. Memory-T-cell-derived interferon-γ instructs potent innate cell activation for protective immunity. Immunity. 2014; 40(6): 974-988.

[87] Mills KHG. TLR-dependent T cell activation in autoimmunity. Nat Rev Immunol. 2011; 11(12): 807-822.

[88] Duan T, Du Y, Xing C, Wang HYY, Wang RF. Toll-like receptor signaling and its role in cell-mediated immunity. Front Immunol. 2022; 13: 812774.

[89] Černý J, Stříž I. Adaptive innate immunity or innate adaptive immunity? Clin Sci (Lond). 2019; 133(14): 1549-1565.

[90] Kumar V. Toll-like receptors in adaptive immunity. In: Kumar V, ed. Toll-like Receptors in Health and Disease. Vol 276. Handbook of Experimental Pharmacology. Springer International Publishing; 2021: 95-131.

[91] Buchta CM, Bishop GA. Toll-like receptors and B cells: functions and mechanisms. Immunol Res. 2014; 59(1-3): 12-22.

[92] Jain S, Chodisetti SB, Agrewala JN. CD40 signaling synergizes with TLR-2 in the BCR independent activation of resting B cells. Sechi LA, ed. PLoS One. 2011; 6(6): e20651.

[93] Iwasaki A, Medzhitov R. Regulation of adaptive immunity by the innate immune system. Science. 2010; 327(5963): 291-295.

[94] Trinchieri G. Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol. 2003; 3(2): 133-146.

[95] Paul WE, Zhu J. How are TH2-type immune responses initiated and amplified? Nat Rev Immunol. 2010; 10(4): 225-235.

[96] Vivier E, Raulet DH, Moretta A, et al. Innate or adaptive immunity? The example of natural killer cells. Science. 2011; 331(6013): 44-49.

[97] Li MO, Flavell RA. TGF-beta: a master of all T cell trades. Cell. 2008; 134(3): 392-404.

[98] Elsner RA, Smita S, Shlomchik MJ. IL-12 induces a B cell-intrinsic IL-12/IFNγ feed-forward loop promoting extrafollicular B cell responses. Nat Immunol. 2024; 25: 1283-1295. Published online June 11, 2024.

[99] Reis ES, Mastellos DC, Hajishengallis G, Lambris JD. New insights into the immune functions of complement. Nat Rev Immunol. 2019; 19(8): 503-516.

[100] Sun L, Wang X, Saredy J, Yuan Z, Yang X, Wang H. Innate-adaptive immunity interplay and redox regulation in immune response. Redox Biol. 2020; 37: 101759.

[101] Cardamone C, Parente R, Feo GD, Triggiani M. Mast cells as effector cells of innate immunity and regulators of adaptive immunity. Immunol Lett. 2016; 178: 10-14.

[102] Chathuranga K, Weerawardhana A, Dodantenna N, Lee JS. Regulation of antiviral innate immune signaling and viral evasion following viral genome sensing. Exp Mol Med. 2021; 53(11): 1647-1668.

[103] Lee HC, Chathuranga K, Lee JS. Intracellular sensing of viral genomes and viral evasion. Exp Mol Med. 2019; 51(12): 1-13.

[104] Xiao Y, Chen X, Wang Z, et al. Succinate is a natural suppressor of antiviral immune response by targeting MAVS. Front Immunol. 2022; 13: 816378.

[105] Turvey SE, Broide DH. Innate immunity. J Allergy Clin Immunol. 2010; 125(2, Supplement 2): S24-S32.

[106] Wimmers F, Donato M, Kuo A, et al. The single-cell epigenomic and transcriptional landscape of immunity to influenza vaccination. Cell. 2021; 184(15): 3915-3935.e21.

[107] Katzmarski N, Domínguez-Andrés J, Cirovic B, et al. Transmission of trained immunity and heterologous resistance to infections across generations. Nat Immunol. 2021; 22(11): 1382-1390.

[108] Bartel Y, Bauer B, Steinle A. Modulation of NK cell function by genetically coupled C-type lectin-like receptor/ligand pairs encoded in the human natural killer gene complex. Front Immunol. 2013; 4: 362.

[109] Ochoa MC, Minute L, Rodriguez I, et al. Antibody-dependent cell cytotoxicity: immunotherapy strategies enhancing effector NK cells. Immunol Cell Biol. 2017; 95(4): 347-355.

[110] Marquardt N, Ivarsson MA, Blom K, et al. The human NK cell response to yellow fever virus 17D is primarily governed by NK cell differentiation independently of NK cell education. J Immunol. 2015; 195(7): 3262-3272.

[111] Zimmer CL, Cornillet M, Solà-Riera C, et al. NK cells are activated and primed for skin-homing during acute dengue virus infection in humans. Nat Commun. 2019; 10(1): 3897.

[112] Scharenberg M, Vangeti S, Kekäläinen E, et al. Influenza A virus infection induces hyperresponsiveness in human lung tissue-resident and peripheral blood NK cells. Front Immunol. 2019; 10: 1116.

[113] Jegaskanda S, Weinfurter JT, Friedrich TC, Kent SJ. Antibody-dependent cellular cytotoxicity is associated with control of pandemic H1N1 influenza virus infection of macaques. J Virol. 2013; 87(10): 5512-5522.

[114] Waggoner SN, Cornberg M, Selin LK, Welsh RM. Natural killer cells act as rheostats modulating antiviral T cells. Nature. 2011; 481(7381): 394-398.

[115] Zapata W, Aguilar-Jiménez W, Pineda-Trujillo N, Rojas W, Estrada H, Rugeles MT. Influence of CCR5 and CCR2 genetic variants in the resistance/susceptibility to HIV in serodiscordant couples from Colombia. AIDS Res Hum Retroviruses. 2013; 29(12): 1594-1603.

[116] Alter G, Martin MP, Teigen N, et al. Differential natural killer cell-mediated inhibition of HIV-1 replication based on distinct KIR/HLA subtypes. J Exp Med. 2007; 204(12): 3027-3036.

[117] Liu N, Pang X, Zhang H, Ji P. The cGAS-STING pathway in bacterial infection and bacterial immunity. Front Immunol. 2022; 12: 814709.

[118] Liu ZZ, Yang YJ, Zhou CK, et al. STING contributes to host defense against staphylococcus aureus pneumonia through suppressing necroptosis. Front Immunol. 2021; 12: 636861.

[119] Zhou Y, Zhao S, Gao X, et al. Staphylococcus aureus induces IFN-β production via a CARMA3-independent mechanism. Pathogens. 2021; 10(3): 300.

[120] Gomes MTR, Guimarães ES, Marinho FV, et al. STING regulates metabolic reprogramming in macrophages via HIF-1α during Brucella infection. Tsolis RM, ed. PLoS Pathog. 2021; 17(5): e1009597.

[121] Tuffs SW, Dufresne K, Rishi A, Walton NR, McCormick JK. Novel insights into the immune response to bacterial T cell superantigens. Nat Rev Immunol. 2024; 24(6): 417-434. Published online January 15, 2024:1-18.

[122] Tuffs SW, Haeryfar SMM, McCormick JK. Manipulation of innate and adaptive immunity by staphylococcal superantigens. Pathogens. 2018; 7(2): 53.

[123] Zeppa JJ, Kasper KJ, Mohorovic I, Mazzuca DM, Haeryfar SMM, McCormick JK. Nasopharyngeal infection by Streptococcus pyogenes requires superantigen-responsive Vβ-specific T cells. Proc Natl Acad Sci USA. 2017; 114(38): 10226-10231.

[124] Lee J, Park N, Park JY, et al. Induction of immunosuppressive CD8⁺/CD25⁺FOXP3⁺ regulatory T cells by suboptimal stimulation with staphylococcal enterotoxin C1. J Immunol. 2018; 200(2): 669-680.

[125] Bjorkander S, Hell L, Johansson MA, et al. Staphylococcus aureus-derived factors induce IL-10, IFN-γ and IL-17A-expressing FOXP3⁺CD161⁺ T-helper cells in a partly monocyte-dependent manner. Sci Rep. 2016; 6: 22083.

[126] Syeda MZ, Hong T, Huang C, Huang W, Mu Q. B cell memory: from generation to reactivation: a multipronged defense wall against pathogens. Cell Death Discov. 2024; 10(1): 1-16.

[127] Liu YJ, Malisan F, deBouteiller O, et al. Within germinal centers, isotype switching of immunoglobulin genes occurs after the onset of somatic mutation. Immunity. 1996; 4(3): 241-250.

[128] Taylor JJ, Pape KA, Jenkins MK. A germinal center-independent pathway generates unswitched memory B cells early in the primary response. J Exp Med. 2012; 209(3): 597-606.

[129] Pape KA, Taylor JJ, Maul RW, Gearhart PJ, Jenkins MK. Different B cell populations mediate early and late memory during an endogenous immune response. Science. 2011; 331(6021): 1203-1207.

[130] Haas KM, Poe JC, Steeber DA, Tedder TF. B-1a and b-1b cells exhibit distinct developmental requirements and have unique functional roles in innate and adaptive immunity to S-pneumoniae. Immunity. 2005; 23(1): 7-18.

[131] Fisher MC, Denning DW. The WHO fungal priority pathogens list as a game-changer. Nat Rev Microbiol. 2023; 21(4): 211-212.

[132] Plato A, Hardison SE, Brown GD. Pattern recognition receptors in antifungal immunity. Semin Immunopathol. 2015; 37(2): 97-106.

[133] Seider K, Brunke S, Schild L, et al. The facultative intracellular pathogen Candida glabrata subverts macrophage cytokine production and phagolysosome maturation. J Immunol. 2011; 187(6): 3072-3086.

[134] Tillmann AT, Strijbis K, Cameron G, et al. Contribution of Fdh3 and Glr1 to glutathione redox state, stress adaptation and virulence in Candida albicans. PLoS One. 2015; 10(6): e0126940.

[135] Schäfer K, Bain JM, Pietro AD, Gow NAR, Erwig LP. Hyphal growth of phagocytosed Fusarium oxysporum causes cell lysis and death of murine macrophages. PLoS One. 2014; 9(7): e101999.

[136] Aguirre J, Hansberg W, Navarro R. Fungal responses to reactive oxygen species. Med Mycol. 2006; 44(s1): 101-107.

[137] Cordero RJB, Casadevall A. Functions of fungal melanin beyond virulence. Fung Biol Rev. 2017; 31(2): 99-112.

[138] den Hertog AL, van Marle J, van Veen HA, et al. Candidacidal effects of two antimicrobial peptides: histatin 5 causes small membrane defects, but LL-37 causes massive disruption of the cell membrane. Biochem J. 2005; 388: 689-695.

[139] Mayer FL, Wilson D, Jacobsen ID, Miramón P, Große K, Hube B. The novel Candida albicans transporter Dur31 is a multi-stage pathogenicity factor. PLoS Pathog. 2012; 8(3): e1002592.

[140] Edgerton M, Koshlukova SE, Araujo MWB, Patel RC, Dong J, Bruenn JA. Salivary histatin 5 and human neutrophil defensin 1 kill Candida albicans via shared pathways. Antimicrob Agents Chemother. 2000; 44(12): 3310-3316.

[141] Loh JT, Lam KP. Fungal infections: immune defense, immunotherapies and vaccines. Adv Drug Deliv Rev. 2023; 196: 114775.

[142] Vudhichamnong K, Walker DM, Ryley HC. The effect of secretory immunoglobulin A on the in-vitro adherence of the yeast Candida albicans to human oral epithelial cells. Arch Oral Biol. 1982; 27(8): 617-621.

[143] Bohler K, Klade H, Poitschek C, Reinthaller A. Immunohistochemical study of in vivo and in vitro IgA coating of candida species in vulvovaginal candidiasis. Sex Transm Infect. 1994; 70(3): 182-186.

[144] Li S-J, Wu Y-L, Chen J-H, Shen S-Y, Duan J, Xu HE. Autoimmune diseases: targets, biology, and drug discovery. Acta Pharmacol Sin. 2024; 45(4): 674-685.

[145] Hogquist KA, Baldwin TA, Jameson SC. Central tolerance: learning self-control in the thymus. Nat Rev Immunol. 2005; 5(10): 772-782.

[146] Bluestone JA, Anderson M. Tolerance in the age of immunotherapy. N Engl J Med. 2020; 383(12): 1156-1166.

[147] Pisetsky DS. Pathogenesis of autoimmune disease. Nat Rev Nephrol. 2023; 19(8): 509-524.

[148] Kant S, Kronbichler A, Sharma P, Geetha D. Advances in understanding of pathogenesis and treatment of immune-mediated kidney disease: a review. Am J Kidney Dis. 2022; 79(4): 582-600.

[149] Sumida TS, Cheru NT, Hafler DA. The regulation and differentiation of regulatory T cells and their dysfunction in autoimmune diseases. Nat Rev Immunol. 2024; 24(7): 503-517. Published online February 19, 2024:1-15.

[150] Sims EK, Mirmira RG, Evans-Molina C. The role of beta-cell dysfunction in early type 1 diabetes. Curr Opin Endocrinol Diabetes Obes. 2020; 27(4): 215-224.

[151] Mackern-Oberti JP, Llanos C, Vega F, et al. Role of dendritic cells in the initiation, progress and modulation of systemic autoimmune diseases. Autoimmun Rev. 2015; 14(2): 127-139.

[152] Kilmon MA, Wagner NJ, Garland AL, et al. Macrophages prevent the differentiation of autoreactive B cells by secreting CD40 ligand and interleukin-6. Blood. 2007; 110(5): 1595-1602.

[153] Hejrati A, Rafiei A, Soltanshahi M, et al. Innate immune response in systemic autoimmune diseases: a potential target of therapy. Inflammopharmacol. 2020; 28(6): 1421-1438.

[154] Kolaczkowska E, Kubes P. Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol. 2013; 13(3): 159-175.

[155] Hagberg N, Berggren O, Leonard D, et al. IFN-α production by plasmacytoid dendritic cells stimulated with RNA-containing immune complexes is promoted by NK cells via MIP-1β and LFA-1. J Immunol. 2011; 186(9): 5085-5094.

[156] Fagone P, Mangano K, Mammana S, et al. Acceleration of SLE-like syndrome development in NZBxNZW F1 mice by beta-glucan. Lupus. 2014; 23(4): 407-411.

[157] Idborg H, Oke V. Cytokines as biomarkers in systemic lupus erythematosus: value for diagnosis and drug therapy. Int J Mol Sci. 2021; 22(21): 11327.

[158] Funes SC, Rios M, Fernández-Fierro A, Di Genaro MS, Kalergis AM. Trained immunity contribution to autoimmune and inflammatory disorders. Front Immunol. 2022; 13: 868343.

[159] Arts RJW, Joosten LAB, Netea MG. The potential role of trained immunity in autoimmune and autoinflammatory disorders. Front Immunol. 2018; 9: 298.

[160] Taylor HB, Vasu C. Impact of prebiotic β-glucan treatment at juvenile age on the gut microbiota composition and the eventual type 1 diabetes onset in non-obese diabetic mice. Front Nutr. 2021; 8: 769341.

[161] Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013; 39(1): 1-10.

[162] Mellman I, Chen DS, Powles T, Turley SJ. The cancer-immunity cycle: indication, genotype, and immunotype. Immunity. 2023; 56(10): 2188-2205.

[163] Hegde PS, Chen DS. Top 10 challenges in cancer immunotherapy. Immunity. 2020; 52(1): 17-35.

[164] Mariathasan S, Turley SJ, Nickles D, et al. TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature. 2018; 554(7693): 544-548.

[165] Fridman WH, Meylan M, Pupier G, Calvez A, Hernandez I, Sautès-Fridman C. Tertiary lymphoid structures and B cells: an intratumoral immunity cycle. Immunity. 2023; 56(10): 2254-2269.

[166] de Visser KE, Joyce JA. The evolving tumor microenvironment: from cancer initiation to metastatic outgrowth. Cancer Cell. 2023; 41(3): 374-403.

[167] Tang L, Huang Z, Mei H, Hu Y. Immunotherapy in hematologic malignancies: achievements, challenges and future prospects. Signal Transduct Target Ther. 2023; 8(1): 1-39.

[168] Bachireddy P, Burkhardt UE, Rajasagi M, Wu CJ. Haematological malignancies: at the forefront of immunotherapeutic innovation. Nat Rev Cancer. 2015; 15(4): 201-215.

[169] Weinhäuser I, Pereira-Martins DA, Almeida LY, et al. M2 macrophages drive leukemic transformation by imposing resistance to phagocytosis and improving mitochondrial metabolism. Sci Adv. 2023; 9(15): eadf8522.

[170] Chao MP, Takimoto CH, Feng DD, et al. Therapeutic targeting of the macrophage immune checkpoint CD47 in myeloid malignancies. Front Oncol. 2020; 9: 1380.

[171] Tran Janco JM, Lamichhane P, Karyampudi L, Knutson KL. Tumor-infiltrating dendritic cells in cancer pathogenesis. J Immunol. 2015; 194(7): 2985-2991.

[172] Kline D, MacNabb B, Chen X, Chan W, Fosco D, Kline J. CD8α + dendritic cells dictate leukemia-specific CD8 + T cell fates. J Immunol. 2018; 201: ji1801184.

[173] Mohty M, Blaise D, Faucher C, et al. Impact of plasmacytoid dendritic cells on outcome after reduced-intensity conditioning allogeneic stem cell transplantation. Leukemia. 2005; 19: 1-6.

[174] Perzolli A, Koedijk JB, Zwaan CM, Heidenreich O. Targeting the innate immune system in pediatric and adult AML. Leukemia. 2024; 38(6): 1191-1201. Published online March 8, 2024:1-11.

[175] Curran EK, Godfrey J, Kline J. Mechanisms of immune tolerance in leukemia and lymphoma. Trends Immunol. 2017; 38(7): 513-525.

[176] Blimark C, Holmberg E, Mellqvist UH, et al. Multiple myeloma and infections: a population-based study on 9253 multiple myeloma patients. Haematologica. 2015; 100(1): 107-113.

[177] Suen H, Brown R, Yang S, et al. Multiple myeloma causes clonal T-cell immunosenescence: identification of potential novel targets for promoting tumour immunity and implications for checkpoint blockade. Leukemia. 2016; 30(8): 1716-1724.

[178] Bascones-Martinez A, Mattila R, Gomez-Font R, Meurman JH. Immunomodulatory drugs: oral and systemic adverse effects. Med Oral Patol Oral Cir Bucal. 2014; 19(1): e24-e31.

[179] Wallis RS, O’Garra A, Sher A, Wack A. Host-directed immunotherapy of viral and bacterial infections: past, present and future. Nat Rev Immunol. 2023; 23(2): 121-133.

[180] Park A, Iwasaki A. Type I and type III interferons—induction, signaling, evasion, and application to combat COVID-19. Cell Host Microbe. 2020; 27(6): 870-878.

[181] Wang N, Zhan Y, Zhu L, et al. Retrospective multicenter cohort study shows early interferon therapy is associated with favorable clinical responses in COVID-19 patients. Cell Host Microbe. 2020; 28(3): 455-464.e2.

[182] WHO Solidarity Trial Consortium, Pan H, Peto R, et al. Repurposed antiviral drugs for Covid-19 - Interim WHO solidarity trial results. N Engl J Med. 2021; 384(6): 497-511.

[183] Garcia-del-Barco D, Risco-Acevedo D, Berlanga-Acosta J, Martos-Benítez FD, Guillén-Nieto G. Revisiting pleiotropic effects of type i interferons: rationale for its prophylactic and therapeutic use against SARS-CoV-2. Front Immunol. 2021; 12: 655528.

[184] Prokunina-Olsson L, Alphonse N, Dickenson RE, et al. COVID-19 and emerging viral infections: the case for interferon lambda. J Exp Med. 2020; 217(5): e20200653.

[185] Leisman DE, Ronner L, Pinotti R, et al. Cytokine elevation in severe and critical COVID-19: a rapid systematic review, meta-analysis, and comparison with other inflammatory syndromes. Lancet Respir Med. 2020; 8(12): 1233-1244.

[186] Le RQ, Li L, Yuan W, et al. FDA approval summary: tocilizumab for treatment of chimeric antigen receptor T cell-induced severe or life-threatening cytokine release syndrome. Oncologist. 2018; 23(8): 943-947.

[187] Chen G, Hu X, Huang Y, et al. Role of the immune system in liver transplantation and its implications for therapeutic interventions. MedComm. 2023; 4(6): e444.

[188] Cavalli G, Larcher A, Tomelleri A, et al. Interleukin-1 and interleukin-6 inhibition compared with standard management in patients with COVID-19 and hyperinflammation: a cohort study. Lancet Rheumatol. 2021; 3(4): e253-e261.

[189] Yi M, Li T, Niu M, et al. Exploiting innate immunity for cancer immunotherapy. Mol Cancer. 2023; 22(1): 187.

[190] Chin EN, Sulpizio A, Lairson LL. Targeting STING to promote antitumor immunity. Trends Cell Biol. 2023; 33(3): 189-203.

[191] Le Naour J, Galluzzi L, Zitvogel L, Kroemer G, Vacchelli E. Trial watch: tLR3 agonists in cancer therapy. Oncoimmunology. 2020; 9(1): 1771143.

[192] Niu M, Yi M, Wu Y, et al. Synergistic efficacy of simultaneous anti-TGF-β/VEGF bispecific antibody and PD-1 blockade in cancer therapy. J Hematol Oncol. 2023; 16(1): 94.

[193] Gabrilovich DI, Ishida T, Nadaf S, Ohm JE, Carbone DP. Antibodies to vascular endothelial growth factor enhance the efficacy of cancer immunotherapy by improving endogenous dendritic cell function1. Clin Cancer Res. 1999; 5(10): 2963-2970.

[194] Flatekval GF, Sioud M. Modulation of dendritic cell maturation and function with mono-and bifunctional small interfering RNAs targeting indoleamine 2, 3-dioxygenase. Immunology. 2009; 128(1 Suppl): e837-e848.

[195] Huntington ND, Cursons J, Rautela J. The cancer–natural killer cell immunity cycle. Nat Rev Cancer. 2020; 20(8): 437-454.

[196] Bald T, Krummel MF, Smyth MJ, Barry KC. The NK cell–cancer cycle: advances and new challenges in NK cell–based immunotherapies. Nat Immunol. 2020; 21(8): 835-847.

[197] Takvorian T, Canellos GP, Ritz J, et al. Prolonged disease-free survival after autologous bone marrow transplantation in patients with non-Hodgkin’s lymphoma with a poor prognosis. N Engl J Med. 1987; 316(24): 1499-1505.

[198] Leivas A, Perez-Martinez A, Blanchard MJ, et al. Novel treatment strategy with autologous activated and expanded natural killer cells plus anti-myeloma drugs for multiple myeloma. Oncoimmunology. 2016; 5(12): e1250051.

[199] Shimasaki N, Jain A, Campana D. NK cells for cancer immunotherapy. Nat Rev Drug Discov. 2020; 19(3): 200-218.

[200] Thangaraj JL, Ahn SY, Jung SH, et al. Expanded natural killer cells augment the antimyeloma effect of daratumumab, bortezomib, and dexamethasone in a mouse model. Cell Mol Immunol. 2021; 18(7): 1652-1661.

[201] Wang X, Yang X, Yuan X, Wang W, Wang Y. Chimeric antigen receptor-engineered NK cells: new weapons of cancer immunotherapy with great potential. Exp Hematol Oncol. 2022; 11(1): 85.

[202] Liu E, Marin D, Banerjee P, et al. Use of CAR-Transduced natural killer cells in CD19-positive lymphoid tumors. N Engl J Med. 2020; 382(6): 545-553.

[203] Deuse T, Hu X, Agbor-Enoh S, et al. The SIRPα-CD47 immune checkpoint in NK cells. J Exp Med. 2021; 218(3): e20200839.

[204] Korde N, Carlsten M, Lee MJ, et al. A phase II trial of pan-KIR2D blockade with IPH2101 in smoldering multiple myeloma. Haematologica. 2014; 99(6): e81-e83.

[205] Gabrilovich DI, Ostrand-Rosenberg S, Bronte V. Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol. 2012; 12(4): 253-268.

[206] Li K, Shi H, Zhang B, et al. Myeloid-derived suppressor cells as immunosuppressive regulators and therapeutic targets in cancer. Signal Transduct Target Ther. 2021; 6(1): 362.

[207] Greene S, Robbins Y, Mydlarz WK, et al. Inhibition of MDSC trafficking with SX-682, a CXCR1/2 inhibitor, enhances NK-cell immunotherapy in head and neck cancer models. Clin Cancer Res. 2020; 26(6): 1420-1431.

[208] Kinoshita R, Sato H, Yamauchi A, et al. Newly developed anti-S100A8/A9 monoclonal antibody efficiently prevents lung tropic cancer metastasis. Int J Cancer. 2019; 145(2): 569-575.

[209] Borges GSM, Lima FA, Carneiro G, Goulart GAC, Ferreira LAM. All-trans retinoic acid in anticancer therapy: how nanotechnology can enhance its efficacy and resolve its drawbacks. Expert Opin Drug Deliv. 2021; 18(10): 1335-1354.

[210] Mirza N, Fishman M, Fricke I, et al. All-trans-retinoic acid improves differentiation of myeloid cells and immune response in cancer patients. Cancer Res. 2006; 66(18): 9299-9307.

[211] Veltman JD, Lambers MEH, van Nimwegen M, et al. COX-2 inhibition improves immunotherapy and is associated with decreased numbers of myeloid-derived suppressor cells in mesothelioma. Celecoxib influences MDSC function. BMC Cancer. 2010; 10: 464.

[212] Rivera Vargas T, Apetoh L. Can immunogenic chemotherapies relieve cancer cell resistance to immune checkpoint inhibitors? Front Immunol. 2019; 10: 1181.

[213] Fultang L, Panetti S, Ng M, et al. MDSC targeting with Gemtuzumab ozogamicin restores T cell immunity and immunotherapy against cancers. EBioMedicine. 2019; 47: 235-246.

[214] Khatoon N, Zhang Z, Zhou C, Chu M. Macrophage membrane coated nanoparticles: a biomimetic approach for enhanced and targeted delivery. Biomater Sci. 2022; 10(5): 1193-1208.

[215] Allavena P, Palmioli A, Avigni R, Sironi M, La Ferla B, Maeda A. PLGA based nanoparticles for the monocyte-mediated anti-tumor drug delivery system. J Biomed Nanotechnol. 2020; 16(2): 212-223.

[216] Pan K, Farrukh H, Chittepu VCSR, Xu H, Pan CX, Zhu Z. CAR race to cancer immunotherapy: from CAR T, CAR NK to CAR macrophage therapy. J Exp Clin Cancer Res. 2022; 41(1): 119.

[217] Morrissey MA, Williamson AP, Steinbach AM, et al. Chimeric antigen receptors that trigger phagocytosis. eLife. 2018; 7: e36688.

[218] Klichinsky M, Ruella M, Shestova O, et al. Human chimeric antigen receptor macrophages for cancer immunotherapy. Nat Biotechnol. 2020; 38(8): 947-953.

[219] Wang S, Yang Y, Ma P, et al. CAR-macrophage: an extensive immune enhancer to fight cancer. EBioMedicine. 2022; 76: 103873.

[220] Kang M, Lee SH, Kwon M, et al. Nanocomplex-mediated in vivo programming to chimeric antigen receptor-M1 macrophages for cancer therapy. Adv Mater. 2021; 33(43): e2103258.

[221] Sharma P, Goswami S, Raychaudhuri D, et al. Immune checkpoint therapy—current perspectives and future directions. Cell. 2023; 186(8): 1652-1669.

[222] Freeman GJ, Long AJ, Iwai Y, et al. Engagement of the Pd-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000; 192(7): 1027-1034.

[223] Dong H, Strome SE, Salomao DR, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002; 8(8): 793-800.

[224] Sharpe AH, Pauken KE. The diverse functions of the PD1 inhibitory pathway. Nat Rev Immunol. 2018; 18(3): 153-167.

[225] Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012; 366(26): 2443-2454.

[226] Carthon BC, Wolchok JD, Yuan J, et al. Preoperative CTLA-4 blockade: tolerability and immune monitoring in the setting of a presurgical clinical trial. Clin Cancer Res. 2010; 16(10): 2861-2871.

[227] Wei SC, Levine JH, Cogdill AP, et al. Distinct cellular mechanisms underlie anti-CTLA-4 and anti-PD-1 checkpoint blockade. Cell. 2017; 170(6): 1120-1133.e17.

[228] Schadendorf D, Hodi FS, Robert C, et al. Pooled analysis of long-term survival data from phase II and phase III trials of ipilimumab in unresectable or metastatic melanoma. JCO. 2015; 33(17): 1889-1894.

[229] Guy C, Mitrea DM, Chou PC, et al. LAG3 associates with TCR–CD3 complexes and suppresses signaling by driving co-receptor–Lck dissociation. Nat Immunol. 2022; 23(5): 757-767.

[230] Baker DJ, Arany Z, Baur JA, Epstein JA, June CH. CAR T therapy beyond cancer: the evolution of a living drug. Nature. 2023; 619(7971): 707-715.

[231] Melenhorst JJ, Chen GM, Wang M, et al. Decade-long leukaemia remissions with persistence of CD4+ CAR T cells. Nature. 2022; 602(7897): 503-509.

[232] Cappell KM, Kochenderfer JN. Long-term outcomes following CAR T cell therapy: what we know so far. Nat Rev Clin Oncol. 2023; 20(6): 359-371.

[233] Abramson JS, Palomba ML, Gordon LI, et al. Two-year follow-up of lisocabtagene maraleucel in relapsed or refractory large B-cell lymphoma in TRANSCEND NHL 001. Blood. 2024; 143(5): 404-416.

[234] Frey NV, Shaw PA, Hexner EO, et al. Optimizing chimeric antigen receptor T-cell therapy for adults with acute lymphoblastic leukemia. J Clin Oncol. 2020; 38(5): 415-422.

[235] Zhao WH, Wang BY, Chen LJ, et al. Four-year follow-up of LCAR-B38M in relapsed or refractory multiple myeloma: a phase 1, single-arm, open-label, multicenter study in China (LEGEND-2). J Hematol Oncol. 2022; 15(1): 86.

[236] Poria R, Kala D, Nagraik R, et al. Vaccine development: current trends and technologies. Life Sci. 2024; 336: 122331.

[237] Reddy VS, Barry MA. Structural organization and protein-protein interactions in human adenovirus capsid. In: Harris JR, Marles-Wright J, eds. Macromolecular Protein Complexes III: Structure and Function. Springer International Publishing; 2021: 503-518.

[238] Teigler JE, Iampietro MJ, Barouch DH. Vaccination with adenovirus serotypes 35, 26, and 48 elicits higher levels of innate cytokine responses than adenovirus serotype 5 in rhesus monkeys. J Virol. 2012; 86(18): 9590-9598.

[239] Quinn KM, Zak DE, Costa A, et al. Antigen expression determines adenoviral vaccine potency independent of IFN and STING signaling. J Clin Invest. 2015; 125(3): 1129-1146.

[240] Rhee EG, Blattman JN, Kasturi SP, et al. Multiple innate immune pathways contribute to the immunogenicity of recombinant adenovirus vaccine vectors. J Virol. 2011; 85(1): 315-323.

[241] Marquez-Martinez S, Vijayan A, Khan S, Zahn R. Cell entry and innate sensing shape adaptive immune responses to adenovirus-based vaccines. Curr Opin Immunol. 2023; 80: 102282.

[242] Baden LR, El Sahly HM, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021; 384(5): 403-416.

[243] Pardi N, Hogan MJ, Porter FW, Weissman D. mRNA vaccines—a new era in vaccinology. Nat Rev Drug Discov. 2018; 17(4): 261-279.

[244] Pepini T, Pulichino AM, Carsillo T, et al. Induction of an IFN-mediated antiviral response by a self-amplifying RNA vaccine: implications for vaccine design. J Immunol. 2017; 198(10): 4012-4024.

[245] De Beuckelaer A, Grooten J, De Koker S. Type I interferons modulate CD8+ T cell immunity to mRNA vaccines. Trends Mol Med. 2017; 23(3): 216-226.

[246] Wiesel M, Crouse J, Bedenikovic G, Sutherland A, Joller N, Oxenius A. Type-I IFN drives the differentiation of short-lived effector CD8+ T cells in vivo. Eur J Immunol. 2012; 42(2): 320-329.

[247] Terawaki S, Chikuma S, Shibayama S, et al. IFN-α directly promotes programmed cell death-1 transcription and limits the duration of T cell-mediated immunity. J Immunol. 2011; 186(5): 2772-2779.

[248] Connors J, Cusimano G, Mege N, et al. Using the power of innate immunoprofiling to understand vaccine design, infection, and immunity. Hum Vaccin Immunother. 2023; 19(3): 2267295.

[249] Connors J, Taramangalam B, Cusimano G, et al. Aging alters antiviral signaling pathways resulting in functional impairment in innate immunity in response to pattern recognition receptor agonists. GeroScience. 2022; 44(5): 2555-2572.

[250] Ren H, Jia W, Xie Y, Yu M, Chen Y. Adjuvant physiochemistry and advanced nanotechnology for vaccine development. Chem Soc Rev. 2023; 52(15): 5172-5254.

[251] O’Hagan DT, Ott GS, De Gregorio E, Seubert A. The mechanism of action of MF59 - an innately attractive adjuvant formulation. Vaccine. 2012; 30(29): 4341-4348.

[252] Huleatt JW, Jacobs AR, Tang J, et al. Vaccination with recombinant fusion proteins incorporating Toll-like receptor ligands induces rapid cellular and humoral immunity. Vaccine. 2007; 25(4): 763-775.

[253] Medzhitov R, Iwasaki A. Exploring new perspectives in immunology. Cell. 2024; 187(9): 2079-2094.

[254] Udit S, Blake K, Chiu I. Somatosensory and autonomic neuronal regulation of the immune response. Nat Rev Neurosci. 2022; 23(3): 157-171.

[255] Grzywa TM, Nowis D, Golab J. The role of CD71+ erythroid cells in the regulation of the immune response. Pharmacol Ther. 2021; 228: 107927.

[256] Iorio R. Myasthenia gravis: the changing treatment landscape in the era of molecular therapies. Nat Rev Neurol. 2024; 20(2): 84-98.

[257] Kamburova EG, Koenen HJPM, Borgman KJE, ten Berge IJ, Joosten I, Hilbrands LB. A single dose of rituximab does not deplete B cells in secondary lymphoid organs but alters phenotype and function. Am J Transplant. 2013; 13(6): 1503-1511.

[258] Kosmas C, Stamatopoulos K, Stavroyianni N, Tsavaris N, Papadaki T. Anti-CD20-based therapy of B cell lymphoma: state of the art. Leukemia. 2002; 16(10): 2004-2015.

[259] Holers VM. Complement and its receptors: new insights into human disease. Annu Rev Immunol. 2014; 32: 433-459.

[260] Li Y, Yi JS, Howard JF, Chopra M, Russo MA, Guptill JT. Cellular changes in eculizumab early responders with generalized myasthenia gravis. Clin Immunol. 2021; 231: 108830.

[261] Dubois EA, Cohen AF. Eculizumab. Br J Clin Pharmacol. 2009; 68(3): 318-319.

[262] Pittock SJ, Berthele A, Fujihara K, et al. Eculizumab in aquaporin-4-positive neuromyelitis optica spectrum disorder. N Engl J Med. 2019; 381(7): 614-625.

[263] Alnefaie A, Albogami S, Asiri Y, et al. Chimeric antigen receptor T-cells: an overview of concepts, applications, limitations, and proposed solutions. Front Bioeng Biotechnol. 2022; 10: 797440.

[264] Granit V, Benatar M, Kurtoglu M, et al. Safety and clinical activity of autologous RNA chimeric antigen receptor T-cell therapy in myasthenia gravis (MG-001): a prospective, multicentre, open-label, non-randomised phase 1b/2a study. Lancet Neurol. 2023; 22(7): 578-590.

[265] Baysoy A, Bai Z, Satija R, Fan R. The technological landscape and applications of single-cell multi-omics. Nat Rev Mol Cell Biol. 2023; 24(10): 695-713.

[266] Yue J, Liu Y, Zhao M, Bi X, Li G, Liang W. The R&D landscape for infectious disease vaccines. Nat Rev Drug Discov. 2023; 22(11): 867-868.

[267] Jackson NAC, Kester KE, Casimiro D, Gurunathan S, DeRosa F. The promise of mRNA vaccines: a biotech and industrial perspective. NPJ Vaccines. 2020; 5: 11.

[268] Guan S, Rosenecker J. Nanotechnologies in delivery of mRNA therapeutics using nonviral vector-based delivery systems. Gene Ther. 2017; 24(3): 133-143.

[269] Zhang G, Tang T, Chen Y, Huang X, Liang T. mRNA vaccines in disease prevention and treatment. Signal Transduct Target Ther. 2023; 8(1): 1-30.

[270] Wang DR, Wu XL, Sun YL. Therapeutic targets and biomarkers of tumor immunotherapy: response versus non-response. Signal Transduct Target Ther. 2022; 7(1): 1-27.

[271] Duan Z, Yang D, Yuan P, Dai X, Chen G, Wu D. Advances, opportunities and challenges in developing therapeutic cancer vaccines. Crit Rev Oncol Hematol. 2024; 193: 104198.

[272] Hui E. Immune checkpoint inhibitors. J Cell Biol. 2019; 218(3): 740-741.

[273] Curran CS, Kopp JB. PD-1 immunobiology in glomerulonephritis and renal cell carcinoma. BMC Nephrol. 2021; 22(1): 80.

[274] Xu-Monette ZY, Zhou J, Young KH. PD-1 expression and clinical PD-1 blockade in B-cell lymphomas. Blood. 2018; 131(1): 68-83.

[275] Lee N, Zakka LR, Mihm MC, Schatton T. Tumour-infiltrating lymphocytes in melanoma prognosis and cancer immunotherapy. Pathology (Phila). 2016; 48(2): 177-187.

[276] Wagner DL, Fritsche E, Pulsipher MA, et al. Immunogenicity of CAR T cells in cancer therapy. Nat Rev Clin Oncol. 2021; 18(6): 379-393.

[277] Huang X, Yang Y. Driving an improved CAR for cancer immunotherapy. J Clin Invest. 2016; 126(8): 2795-2798.

[278] Liu E, Tong Y, Dotti G, et al. Cord blood NK cells engineered to express IL-15 and a CD19-targeted CAR show long-term persistence and potent antitumor activity. Leukemia. 2018; 32(2): 520-531.

[279] Waldmann TA, Dubois S, Miljkovic MD, Conlon KC. IL-15 in the combination immunotherapy of cancer. Front Immunol. 2020; 11: 868.

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