Skip to content
2000
image of Tumor-embedded Immunity and TRM Cell Functions in Cancer

Abstract

In the ongoing battle between the immune system and cancer, a unique subset of T cells has quietly emerged as a key player. Tissue-Resident Memory T (TRM) cells, strategically positioned within tissues, are redefining our understanding of localized immune defense and tumor control. This review aims to bridge this knowledge gap by synthesizing current concepts of T cell immune surveillance with foundational aspects of TRM cell biology. We explored clinical evidence supporting the prognostic and therapeutic relevance of TRM cells in various cancer contexts, including their emerging roles in enhancing responses to immunotherapy. Furthermore, we discussed innovative strategies that exploit TRM-phenotype cells for patient stratification, disease staging, and therapeutic development. Key challenges such as the absence of standardized T cell nomenclature and the limited understanding of how TRM markers relate to tumor biology are critically examined. By integrating basic science and clinical observations, this review provides a comprehensive overview of the field and highlights promising avenues for future research to harness TRM cells in precision oncology.

Loading

Article metrics loading...

/content/journals/mrmc/10.2174/0113895575412480251114071338
2026-01-22
2026-01-29
Loading full text...

Full text loading...

References

  1. Finn O. Immuno-oncology: Understanding the function and dysfunction of the immune system in cancer. Annals of Oncology 2012 23 viii6 viii9
    [Google Scholar]
  2. Ventola C.L. Cancer immunotherapy, part 1: Current strategies and agents. P&T 2017 42 6 375 383 28579724
    [Google Scholar]
  3. Zhang Y. Zhang Z. The history and advances in cancer immunotherapy: Understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications. Cell. Mol. Immunol. 2020 17 8 807 821 10.1038/s41423‑020‑0488‑6 32612154
    [Google Scholar]
  4. Schmetterer K.G. Neunkirchner A. Pickl W.F. Naturally occurring regulatory T cells: markers, mechanisms, and manipulation. FASEB J. 2012 26 6 2253 2276 10.1096/fj.11‑193672 22362896
    [Google Scholar]
  5. Schaefer C. Kim G.G. Albers A. Hoermann K. Myers E.N. Whiteside T.L. Characteristics of CD4+CD25+ regulatory T cells in the peripheral circulation of patients with head and neck cancer. Br. J. Cancer 2005 92 5 913 920 10.1038/sj.bjc.6602407 15714205
    [Google Scholar]
  6. Li S. Gowans E.J. Chougnet C. Plebanski M. Dittmer U. Natural regulatory T cells and persistent viral infection. J. Virol. 2008 82 1 21 30 10.1128/JVI.01768‑07 17855537
    [Google Scholar]
  7. Peña-Romero A.C. Orenes-Piñero E. Dual effect of immune cells within tumour microenvironment: Pro-and anti-tumour effects and their triggers. Cancers 2022 14 7 1681 10.3390/cancers14071681 35406451
    [Google Scholar]
  8. Ramesh P. Shivde R. Jaishankar D. Saleiro D. Le Poole I.C. A palette of cytokines to measure anti-tumor efficacy of T cell-based therapeutics. Cancers 2021 13 4 821 10.3390/cancers13040821 33669271
    [Google Scholar]
  9. Halle S. Halle O. Förster R. Mechanisms and dynamics of T cell-mediated cytotoxicity in vivo. Trends Immunol. 2017 38 6 432 443 10.1016/j.it.2017.04.002 28499492
    [Google Scholar]
  10. Dijkgraaf F.E. Matos T.R. Hoogenboezem M. Toebes M. Vredevoogd D.W. Mertz M. van den Broek B. Song J.Y. Teunissen M.B.M. Luiten R.M. Beltman J.B. Schumacher T.N. Tissue patrol by resident memory CD8+ T cells in human skin. Nat. Immunol. 2019 20 6 756 764 10.1038/s41590‑019‑0404‑3 31110315
    [Google Scholar]
  11. Gavil N.V. Cheng K. Masopust D. Resident memory T cells and cancer. Immunity 2024 57 8 1734 1751 10.1016/j.immuni.2024.06.017 39142275
    [Google Scholar]
  12. Long B. Zhou S. Gao Y. Fan K. Lai J. Yao C. Li J. Xu X. Yu S. Tissue-Resident Memory T Cells in Allergy. Clin. Rev. Allergy Immunol. 2024 66 1 64 75 10.1007/s12016‑024‑08982‑8 38381299
    [Google Scholar]
  13. Ward-Hartstonge K.A. Kemp R.A. Regulatory T‐cell heterogeneity and the cancer immune response. Clin. Transl. Immunology 2017 6 9 e154 10.1038/cti.2017.43 28983402
    [Google Scholar]
  14. Mami-Chouaib F. Blanc C. Corgnac S. Hans S. Malenica I. Granier C. Tihy I. Tartour E. Resident memory T cells, critical components in tumor immunology. J. Immunother. Cancer 2018 6 1 87 10.1186/s40425‑018‑0399‑6 30180905
    [Google Scholar]
  15. Molodtsov A. Turk M.J. Tissue resident CD8 memory T cell responses in cancer and autoimmunity. Front. Immunol. 2018 9 2810 10.3389/fimmu.2018.02810 30555481
    [Google Scholar]
  16. Sadeghi Rad H. Monkman J. Warkiani M.E. Ladwa R. O’Byrne K. Rezaei N. Kulasinghe A. Understanding the tumor microenvironment for effective immunotherapy. Med. Res. Rev. 2021 41 3 1474 1498 10.1002/med.21765 33277742
    [Google Scholar]
  17. Sell S. Cancer immunotherapy: Breakthrough or “deja vu, all over again”? Tumour Biol. 2017 39 6 10.1177/1010428317707764 28639883
    [Google Scholar]
  18. Nagarajan D. Towards the development of HAGE-based vaccines for the treatment of patients with triple negative breast cancers. United Kingdom Nottingham Trent University 2018
    [Google Scholar]
  19. Garrido F. The Major Histocompatibility Complex (MHC/ HLA) in Medicine Apersonal recollection, springe nature 2024
    [Google Scholar]
  20. Wang H. Strategies for Prevention of Antibody Mediated Allograft Rejection. School of Graduate and Postdoctoral Studies, University of Western Ontario 2009
    [Google Scholar]
  21. Wong P. Pamer E.G. CD8 T cell responses to infectious pathogens. Annu. Rev. Immunol. 2003 21 1 29 70 10.1146/annurev.immunol.21.120601.141114 12414723
    [Google Scholar]
  22. Wilczynski J.R. Nowak M. Cancer immunoediting: Elimination, equilibrium, and immune escape in solid tumors. Interaction of Immune and Cancer Cells 2014 1 57 10.1007/978‑3‑030‑91311‑3_1
    [Google Scholar]
  23. Baird T. Using Tumour Evolution to Understand the Epigenetic and Transcriptional Adaptations of Cancer to Host Immunity. University of Cambridge 2024
    [Google Scholar]
  24. DeLucia D.C. Lee J.K. Development of cancer immunotherapies. Cancer Immunotherapies: Solid Tumors and Hematologic Malignancies. Springer 2022 10.1007/978‑3‑030‑96376‑7_1
    [Google Scholar]
  25. Paijens S.T. Vledder A. de Bruyn M. Nijman H.W. Tumor-infiltrating lymphocytes in the immunotherapy era. Cell. Mol. Immunol. 2021 18 4 842 859 10.1038/s41423‑020‑00565‑9 33139907
    [Google Scholar]
  26. Verdeil G. From T cell “exhaustion” to anti-cancer immunity. Biochimica et Biophysica Acta. (BBA) - Reviews on Cancer 2016 1865 1 49 57
    [Google Scholar]
  27. Filiano A.J. Gadani S.P. Kipnis J. How and why do T cells and their derived cytokines affect the injured and healthy brain? Nat. Rev. Neurosci. 2017 18 6 375 384 10.1038/nrn.2017.39 28446786
    [Google Scholar]
  28. Ahmed H. Role of T cells in cancer immunotherapy: Opportunities and challenges. Cancer Pathog Ther. 2023 1 02 116 126 10.1016/j.cpt.2022.12.002
    [Google Scholar]
  29. Sims S. Willberg C. Klenerman P. MHC–peptide tetramers for the analysis of antigen-specific T cells. Expert Rev. Vaccines 2010 9 7 765 774 10.1586/erv.10.66 20624049
    [Google Scholar]
  30. McLane L.M. Abdel-Hakeem M.S. Wherry E.J. CD8 T cell exhaustion during chronic viral infection and cancer. Annu. Rev. Immunol. 2019 37 1 457 495 10.1146/annurev‑immunol‑041015‑055318 30676822
    [Google Scholar]
  31. Fife B.T. Bluestone J.A. Control of peripheral T‐cell tolerance and autoimmunity via the CTLA‐4 and PD‐1 pathways. Immunol. Rev. 2008 224 1 166 182 10.1111/j.1600‑065X.2008.00662.x 18759926
    [Google Scholar]
  32. Weber J. Role of T cells in cancer immunotherapy: Opportunities and challenges. Cancer Pathogenesis and Therapy 2023 1 02 116 126 10.1053/j.seminoncol.2010.09.005
    [Google Scholar]
  33. Lamba N. Ott P.A. Iorgulescu J.B. Use of first-line immune checkpoint inhibitors and association with overall survival among patients with metastatic melanoma in the anti–PD-1 era. JAMA Netw. Open 2022 5 8 e2225459 e2225459 10.1001/jamanetworkopen.2022.25459 36006646
    [Google Scholar]
  34. Jia Y. Liu L. Shan B. Future of immune checkpoint inhibitors: focus on tumor immune microenvironment. Ann. Transl. Med. 2020 8 17 1095 10.21037/atm‑20‑3735 33145314
    [Google Scholar]
  35. Andersen M.H. Schrama D. thor Straten P. Becker J.C. Cytotoxic T cells. J. Invest. Dermatol. 2006 126 1 32 41 10.1038/sj.jid.5700001 16417215
    [Google Scholar]
  36. Dähling S. Type 1 conventional dendritic cells maintain and guide the differentiation of precursors of exhausted T cells in distinct cellular niches. Immunity 2022 55 4 656 670 10.1016/j.immuni.2022.03.006
    [Google Scholar]
  37. Ni L. Potential mechanisms of cancer stem‐like progenitor T‐cell bio‐behaviours. Clin. Transl. Med. 2024 14 8 e1817 10.1002/ctm2.1817 39169517
    [Google Scholar]
  38. Xia Y. The Maintenance of CD4 and CD8 T Cell Response to Persistent Antigens. Dissertation 2022
    [Google Scholar]
  39. Verdon D.J. Mulazzani M. Jenkins M.R. Cellular and molecular mechanisms of CD8+ T cell differentiation, dysfunction and exhaustion. Int. J. Mol. Sci. 2020 21 19 7357 10.3390/ijms21197357 33027962
    [Google Scholar]
  40. Abdel-Hakeem M.S. Manne S. Beltra J.C. Stelekati E. Chen Z. Nzingha K. Ali M.A. Johnson J.L. Giles J.R. Mathew D. Greenplate A.R. Vahedi G. Wherry E.J. Epigenetic scarring of exhausted T cells hinders memory differentiation upon eliminating chronic antigenic stimulation. Nat. Immunol. 2021 22 8 1008 1019 10.1038/s41590‑021‑00975‑5 34312545
    [Google Scholar]
  41. Dumauthioz N. Labiano S. Romero P. Tumor resident memory T cells: New players in immune surveillance and therapy. Front. Immunol. 2018 9 2076 10.3389/fimmu.2018.02076 30258445
    [Google Scholar]
  42. Iijima N. The emerging role of effector functions exerted by tissue-resident memory T cells. Oxf. Open Immunol. 2024 5 1 iqae006 10.1093/oxfimm/iqae006 39193473
    [Google Scholar]
  43. Pan Y. Kupper T.S. Metabolic reprogramming and longevity of tissue-resident memory T cells. Front. Immunol. 2018 9 1347 10.3389/fimmu.2018.01347 29967608
    [Google Scholar]
  44. Pandey P. Khan F. Upadhyay T.K. Maqsood R. Review to understand the crosstalk between immunotherapy and tumor metabolism. Molecules 2023 28 2 862 10.3390/molecules28020862 36677919
    [Google Scholar]
  45. Förster R. Braun A. Worbs T. Lymph node homing of T cells and dendritic cells via afferent lymphatics. Trends Immunol. 2012 33 6 271 280 10.1016/j.it.2012.02.007 22459312
    [Google Scholar]
  46. Masopust D. Picker L.J. Hidden memories: Frontline memory T cells and early pathogen interception. J. Immunol. 2012 188 12 5811 5817 10.4049/jimmunol.1102695 22675215
    [Google Scholar]
  47. Aleksić I. Dopaminergic modulation of phenotypical and functional characteristics of human T lymphocytes: perspectives for nonconventional immunomodulation. Università degli Studi dell'Insubria 2017
    [Google Scholar]
  48. Kok L. Masopust D. Schumacher T.N. The precursors of CD8+ tissue resident memory T cells: from lymphoid organs to infected tissues. Nat. Rev. Immunol. 2022 22 5 283 293 10.1038/s41577‑021‑00590‑3 34480118
    [Google Scholar]
  49. Simmons S. Ishii M. Sphingosine-1-phosphate: a master regulator of lymphocyte egress and immunity. Arch. Immunol. Ther. Exp. (Warsz.) 2014 62 2 103 115 10.1007/s00005‑013‑0264‑8 24276789
    [Google Scholar]
  50. Eggel A. Wyss-Coray T. Parabiosis for the study of age-related chronic disease. Swiss Med. Wkly. 2014 144 w13914 10.4414/smw.2014.13914 24496774
    [Google Scholar]
  51. Chen F.M. Wu L.A. Zhang M. Zhang R. Sun H.H. Homing of endogenous stem/progenitor cells for in situ tissue regeneration: Promises, strategies, and translational perspectives. Biomaterials 2011 32 12 3189 3209 10.1016/j.biomaterials.2010.12.032 21300401
    [Google Scholar]
  52. Hughes E.L. Gavins F.N.E. Troubleshooting methods: Using intravital microscopy in drug research. J. Pharmacol. Toxicol. Methods 2010 61 2 102 112 10.1016/j.vascn.2010.01.004 20097299
    [Google Scholar]
  53. Mikulska M. Lanini S. Gudiol C. Drgona L. Ippolito G. Fernández-Ruiz M. Salzberger B. ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Agents targeting lymphoid cells surface antigens [I]: CD19, CD20 and CD52). Clin. Microbiol. Infect. 2018 24 S71 S82 10.1016/j.cmi.2018.02.003 29447988
    [Google Scholar]
  54. Mueller S.N. Mackay L.K. Tissue-resident memory T cells: local specialists in immune defence. Nat. Rev. Immunol. 2016 16 2 79 89 10.1038/nri.2015.3 26688350
    [Google Scholar]
  55. Steinert E.M. Evaluating memory CD8 T cell quantity, distribution and migration. Dissertations 2016
    [Google Scholar]
  56. Cheng L. Becattini S. Intestinal CD8+ tissue‐resident memory T cells: From generation to function. Eur. J. Immunol. 2022 52 10 1547 1560 10.1002/eji.202149759 35985020
    [Google Scholar]
  57. Jung H. Paust S. Chemokines in the tumor microenvironment: implications for lung cancer and immunotherapy. Front. Immunol. 2024 15 1443366 10.3389/fimmu.2024.1443366 39114657
    [Google Scholar]
  58. Qiu Z. Chu T.H. Sheridan B.S. TGF-β: Many paths to CD103+ CD8 T cell residency. Cells 2021 10 5 989 10.3390/cells10050989 33922441
    [Google Scholar]
  59. Amsen D. van Gisbergen K.P.J.M. Hombrink P. van Lier R.A.W. Tissue-resident memory T cells at the center of immunity to solid tumors. Nat. Immunol. 2018 19 6 538 546 10.1038/s41590‑018‑0114‑2 29777219
    [Google Scholar]
  60. Khanna R. Tumour surveillance: Missing peptides and MHC molecules. Immunol. Cell. Biol. 1998 76 1 20 26 10.1046/j.1440‑1711.1998.00717.x 9553772
    [Google Scholar]
  61. Szabo P.A. Axes of heterogeneity in human tissue‐resident memory T cells. Immunol. Rev. 2023 316 1 23 37 10.1111/imr.13210 37211646
    [Google Scholar]
  62. Chen W. TGF-β Regulation of T Cells. Annu. Rev. Immunol. 2023 41 1 483 512 10.1146/annurev‑immunol‑101921‑045939 36750317
    [Google Scholar]
  63. Gasteiger G. Ataide M. Kastenmüller W. Lymph node – an organ for T‐cell activation and pathogen defense. Immunol. Rev. 2016 271 1 200 220 10.1111/imr.12399 27088916
    [Google Scholar]
  64. Barreto de Albuquerque J. Mueller C. Gungor B. Tissue-Resident T. Cells in Chronic Relapsing–Remitting Intestinal Disorders. Cells 2021 10 8 1882 10.3390/cells10081882 34440651
    [Google Scholar]
  65. Johnson L.A. In sickness and in health: the immunological roles of the lymphatic system. Int. J. Mol. Sci. 2021 22 9 4458 10.3390/ijms22094458 33923289
    [Google Scholar]
  66. Akbaba H. Resident memory T cells. Cells of the Immune System. IntechOpen 2020 10.5772/intechopen.90334
    [Google Scholar]
  67. Kumar B.V. Ma W. Miron M. Granot T. Guyer R.S. Carpenter D.J. Senda T. Sun X. Ho S.H. Lerner H. Friedman A.L. Shen Y. Farber D.L. Human tissue-resident memory T cells are defined by core transcriptional and functional signatures in lymphoid and mucosal sites. Cell Rep. 2017 20 12 2921 2934 10.1016/j.celrep.2017.08.078 28930685
    [Google Scholar]
  68. Mackay L.K. Wynne-Jones E. Freestone D. Pellicci D.G. Mielke L.A. Newman D.M. Braun A. Masson F. Kallies A. Belz G.T. Carbone F.R. T-box transcription factors combine with the cytokines TGF-β and IL-15 to control tissue-resident memory T cell fate. Immunity 2015 43 6 1101 1111 10.1016/j.immuni.2015.11.008 26682984
    [Google Scholar]
  69. Ding Q. Gao Z. Chen K. Zhang Q. Hu S. Zhao L. Inflammation-related epigenetic modification: the bridge between immune and metabolism in type 2 diabetes. Front. Immunol. 2022 13 883410 10.3389/fimmu.2022.883410 35603204
    [Google Scholar]
  70. Corgnac S. Boutet M. Kfoury M. Naltet C. Mami-Chouaib F. The emerging role of CD8+ tissue resident memory T (TRM) cells in antitumor immunity: a unique functional contribution of the CD103 integrin. Front. Immunol. 2018 9 1904 10.3389/fimmu.2018.01904 30158938
    [Google Scholar]
  71. Caccamo N. Joosten S.A. Ottenhoff T.H.M. Dieli F. Atypical human effector/memory CD4+ T cells with a naive-like phenotype. Front. Immunol. 2018 9 2832 10.3389/fimmu.2018.02832 30559746
    [Google Scholar]
  72. Nguyen Q.P. Deng T.Z. Witherden D.A. Goldrath A.W. Origins of CD 4+ circulating and tissue‐resident memory T‐cells. Immunology 2019 157 1 3 12 10.1111/imm.13059 30897205
    [Google Scholar]
  73. Monteiro M.F. Characterization of CD8+ T-cell populations of the human peripheral blood. Portugal Universidade de Lisboa 2006
    [Google Scholar]
  74. Jiang Y. Li Y. Zhu B. T-cell exhaustion in the tumor microenvironment. Cell Death Dis. 2015 6 6 e1792 e1792 10.1038/cddis.2015.162 26086965
    [Google Scholar]
  75. Sakaguchi S. Ono M. Setoguchi R. Yagi H. Hori S. Fehervari Z. Shimizu J. Takahashi T. Nomura T. Foxp3 + CD25+ CD4+ natural regulatory T cells in dominant self‐tolerance and autoimmune disease. Immunol. Rev. 2006 212 1 8 27 10.1111/j.0105‑2896.2006.00427.x 16903903
    [Google Scholar]
  76. Fu J. Sykes M. Emerging concepts of tissue-resident memory T cells in transplantation. Transplantation 2022 106 6 1132 1142 10.1097/TP.0000000000004000 34873129
    [Google Scholar]
  77. Pascutti M.F. Peripheral and systemic antigens elicit an expandable pool of resident memory CD8+ T cells in the bone marrow. Eur. J. Immunol. 2019 49 6 853 872 10.1002/eji.201848003 30891737
    [Google Scholar]
  78. Enamorado M. Khouili S.C. Iborra S. Sancho D. Genealogy, dendritic cell primin g, and differentiation of tissue-resident memory CD8+ T cells. Front. Immunol. 2018 9 1751 10.3389/fimmu.2018.01751 30108585
    [Google Scholar]
  79. Shim Y.A. The regulation of erythroid progenitors and T cells by CD45. University of British Columbia 2020
    [Google Scholar]
  80. Topham D.J. Reilly E.C. Tissue-resident memory CD8+ T cells: from phenotype to function. Front. Immunol. 2018 9 515 10.3389/fimmu.2018.00515 29632527
    [Google Scholar]
  81. Stark R. Wesselink T.H. Behr F.M. Kragten N.A.M. Arens R. Koch-Nolte F. van Gisbergen K.P.J.M. van Lier R.A.W. TRM maintenance is regulated by tissue damage via P2RX7. Sci. Immunol. 2018 3 30 eaau1022 10.1126/sciimmunol.aau1022 30552101
    [Google Scholar]
  82. Netherby-Winslow C.S. Ayers K.N. Lukacher A.E. Balancing Inflammation and Central Nervous System Homeostasis: T Cell Receptor Signaling in Antiviral Brain TRM Formation and Function. Front. Immunol. 2021 11 624144 10.3389/fimmu.2020.624144 33584727
    [Google Scholar]
  83. Emmanuel T. Mistegård J. Bregnhøj A. Johansen C. Iversen L. Tissue-resident memory T cells in skin diseases: A systematic review. Int. J. Mol. Sci. 2021 22 16 9004 10.3390/ijms22169004 34445713
    [Google Scholar]
  84. Cvetkovski F. Transcriptional control of tissue-resident memory T cell generation. Columbia University 2019
    [Google Scholar]
  85. Park C.O. Kupper T.S. The emerging role of resident memory T cells in protective immunity and inflammatory disease. Nat. Med. 2015 21 7 688 697 10.1038/nm.3883 26121195
    [Google Scholar]
  86. Najibi A.J. Mooney D.J. Cell and tissue engineering in lymph nodes for cancer immunotherapy. Adv. Drug Deliv. Rev. 2020 161-162 42 62 10.1016/j.addr.2020.07.023 32750376
    [Google Scholar]
  87. Harrington K.J. Puzanov I. Hecht J.R. Hodi F.S. Szabo Z. Murugappan S. Kaufman H.L. Clinical development of talimogene laherparepvec (T-VEC): a modified herpes simplex virus type-1–derived oncolytic immunotherapy. Expert Rev. Anticancer Ther. 2015 15 12 1389 1403 10.1586/14737140.2015.1115725 26558498
    [Google Scholar]
  88. Larocca C.A. LeBoeuf N.R. Silk A.W. Kaufman H.L. An update on the role of talimogene laherparepvec (T-VEC) in the treatment of melanoma: best practices and future directions. Am. J. Clin. Dermatol. 2020 21 6 821 832 10.1007/s40257‑020‑00554‑8 32767272
    [Google Scholar]
  89. Smazynski J. Deciphering the immunosuppressive landscape of high-grade serous ovarian cancer. Dissertations 2022
    [Google Scholar]
  90. Brummel K. Eerkens A.L. de Bruyn M. Nijman H.W. Tumour-infiltrating lymphocytes: from prognosis to treatment selection. Br. J. Cancer 2023 128 3 451 458 10.1038/s41416‑022‑02119‑4 36564565
    [Google Scholar]
  91. Vella-Chentorycki J.L. Intrinsic and Extrinsic Requirements for Tumor-induced Skin Resident CD8 T Cells. Dartmouth College 2020
    [Google Scholar]
  92. Kumar B.V. Kratchmarov R. Miron M. Carpenter D.J. Senda T. Lerner H. Friedman A. Reiner S.L. Farber D.L. Functional heterogeneity of human tissue-resident memory T cells based on dye efflux capacities. JCI Insight 2018 3 22 e123568 10.1172/jci.insight.123568 30429372
    [Google Scholar]
  93. Gupta G. Dwivedi S. Shukla K.K. Sharma P. Tissue-resident memory cells: New marked shield to fight cancers. Indian J. Clin. Biochem. 2018 33 2 119 120 10.1007/s12291‑018‑0745‑y 29651201
    [Google Scholar]
  94. Khosravi G.R. Mostafavi S. Bastan S. Ebrahimi N. Gharibvand R.S. Eskandari N. Immunologic tumor microenvironment modulators for turning cold tumors hot. Cancer Commun. 2024 44 5 521 553 10.1002/cac2.12539 38551889
    [Google Scholar]
  95. Liu Y.T. Sun Z.J. Turning cold tumors into hot tumors by improving T-cell infiltration. Theranostics 2021 11 11 5365 5386 10.7150/thno.58390 33859752
    [Google Scholar]
  96. Djenidi F. Adam J. Goubar A. Durgeau A. Meurice G. de Montpréville V. Validire P. Besse B. Mami-Chouaib F. CD8+CD103+ tumor-infiltrating lymphocytes are tumor-specific tissue-resident memory T cells and a prognostic factor for survival in lung cancer patients. J. Immunol. 2015 194 7 3475 3486 10.4049/jimmunol.1402711 25725111
    [Google Scholar]
  97. Finn O.J. Cancer vaccines: between the idea and the reality. Nat. Rev. Immunol. 2003 3 8 630 641 10.1038/nri1150 12974478
    [Google Scholar]
  98. Szabo P.A. Levitin H.M. Miron M. Snyder M.E. Senda T. Yuan J. Cheng Y.L. Bush E.C. Dogra P. Thapa P. Farber D.L. Sims P.A. Single-cell transcriptomics of human T cells reveals tissue and activation signatures in health and disease. Nat. Commun. 2019 10 1 4706 10.1038/s41467‑019‑12464‑3 31624246
    [Google Scholar]
  99. Caushi J.X. Zhang J. Ji Z. Vaghasia A. Zhang B. Hsiue E.H.C. Mog B.J. Hou W. Justesen S. Blosser R. Tam A. Anagnostou V. Cottrell T.R. Guo H. Chan H.Y. Singh D. Thapa S. Dykema A.G. Burman P. Choudhury B. Aparicio L. Cheung L.S. Lanis M. Belcaid Z. El Asmar M. Illei P.B. Wang R. Meyers J. Schuebel K. Gupta A. Skaist A. Wheelan S. Naidoo J. Marrone K.A. Brock M. Ha J. Bush E.L. Park B.J. Bott M. Jones D.R. Reuss J.E. Velculescu V.E. Chaft J.E. Kinzler K.W. Zhou S. Vogelstein B. Taube J.M. Hellmann M.D. Brahmer J.R. Merghoub T. Forde P.M. Yegnasubramanian S. Ji H. Pardoll D.M. Smith K.N. Transcriptional programs of neoantigen-specific TIL in anti-PD-1-treated lung cancers. Nature 2021 596 7870 126 132 10.1038/s41586‑021‑03752‑4 34290408
    [Google Scholar]
  100. Yaping W. Zhe W. Zhuling C. Ruolei L. Pengyu F. Lili G. Cheng J. Bo Z. Liuyin L. Guangdong H. Yaoling W. Niuniu H. Rui L. The soldiers needed to be awakened: Tumor-infiltrating immune cells. Front. Genet. 2022 13 988703 10.3389/fgene.2022.988703 36246629
    [Google Scholar]
  101. Pearce H. Croft W. Nicol S.M. Margielewska-Davies S. Powell R. Cornall R. Davis S.J. Marcon F. Pugh M.R. Fennell É. Powell-Brett S. Mahon B.S. Brown R.M. Middleton G. Roberts K. Moss P. Tissue-resident memory t cells in pancreatic ductal adenocarcinoma coexpress PD-1 and TIGIT and functional inhibition is reversible by dual antibody blockade. Cancer Immunol. Res. 2023 11 4 435 449 10.1158/2326‑6066.CIR‑22‑0121 36689623
    [Google Scholar]
  102. Okła K. Farber D.L. Zou W. Tissue-resident memory T cells in tumor immunity and immunotherapy. J. Exp. Med. 2021 218 4 e20201605 10.1084/jem.20201605 33755718
    [Google Scholar]
  103. Webb J.R. Milne K. Watson P. deLeeuw R.J. Nelson B.H. Tumor-infiltrating lymphocytes expressing the tissue resident memory marker CD103 are associated with increased survival in high-grade serous ovarian cancer. Clin. Cancer Res. 2014 20 2 434 444 10.1158/1078‑0432.CCR‑13‑1877 24190978
    [Google Scholar]
  104. Zhou P. Shi H. Huang H. Sun X. Yuan S. Chapman N.M. Connelly J.P. Lim S.A. Sara J. Kc A. Pruett-Miller S.M. Chi H. Single-cell CRISPR screens in vivo map T cell fate regulomes in cancer. Nature 2023 624 7990 154 163 10.1038/s41586‑023‑06733‑x 37968405
    [Google Scholar]
  105. Hu H. Zakharov P.N. Peterson O.J. Unanue E.R. Cytocidal macrophages in symbiosis with CD4 and CD8 T cells cause acute diabetes following checkpoint blockade of PD-1 in NOD mice. Proc. Natl. Acad. Sci. USA 2020 117 49 31319 31330 10.1073/pnas.2019743117 33229539
    [Google Scholar]
  106. Barsch M. Salié H. Mesesan A. Bengsch B. T cells in the heterogeneous tumour immune microenvironment of hepatocellular carcinoma: Implications for immune checkpoint inhibitor therapy. Liver Cancer Int. 2023 4 1 58 72 10.1002/lci2.72
    [Google Scholar]
  107. Byrne A. Savas P. Sant S. Li R. Virassamy B. Luen S.J. Beavis P.A. Mackay L.K. Neeson P.J. Loi S. Tissue-resident memory T cells in breast cancer control and immunotherapy responses. Nat. Rev. Clin. Oncol. 2020 17 6 341 348 10.1038/s41571‑020‑0333‑y 32112054
    [Google Scholar]
  108. Li X. Liu Y. Gui J. Gan L. Xue J. Cell Identity and Spatial Distribution of PD‐1/PD‐L1 Blockade Responders. Adv. Sci. (Weinh.) 2024 11 41 2400702 10.1002/advs.202400702 39248327
    [Google Scholar]
  109. Laumont C.M. Wouters M.C.A. Smazynski J. Gierc N.S. Chavez E.A. Chong L.C. Thornton S. Milne K. Webb J.R. Steidl C. Nelson B.H. Single-cell profiles and prognostic impact of tumor-infiltrating lymphocytes coexpressing CD39, CD103, and PD-1 in ovarian cancer. Clin. Cancer Res. 2021 27 14 4089 4100 10.1158/1078‑0432.CCR‑20‑4394 33963000
    [Google Scholar]
  110. Domenjó Vila E. Immunotherapy of chronic virus infections: Exhausted CD8+ T cell subsets are differentially regulated by XCR1+ DC. 2022
    [Google Scholar]
  111. Gebhardt T. Palendira U. Tscharke D.C. Bedoui S. Tissue‐resident memory T cells in tissue homeostasis, persistent infection, and cancer surveillance. Immunol. Rev. 2018 283 1 54 76 10.1111/imr.12650 29664571
    [Google Scholar]
  112. Varayathu H. Sarathy V. Thomas B.E. Mufti S.S. Naik R. Combination strategies to augment immune check point inhibitors efficacy-implications for translational research. Front. Oncol. 2021 11 559161 10.3389/fonc.2021.559161 34123767
    [Google Scholar]
  113. Hadrup S. Donia M. thor Straten P. Effector CD4 and CD8 T cells and their role in the tumor microenvironment. Cancer Microenviron. 2013 6 2 123 133 10.1007/s12307‑012‑0127‑6 23242673
    [Google Scholar]
  114. Fanale D. Dimino A. Pedone E. Brando C. Corsini L.R. Filorizzo C. Fiorino A. Lisanti M.C. Magrin L. Randazzo U. Bazan Russo T.D. Russo A. Bazan V. Prognostic and predictive role of tumor-infiltrating lymphocytes (TILs) in ovarian cancer. Cancers 2022 14 18 4344 10.3390/cancers14184344 36139508
    [Google Scholar]
  115. Shah P. Enhancing Adoptive Cell Therapy By Augmenting Fitness And Anti-Tumor Function Of Tumor-Infiltrating Lymphocytes. 2021
    [Google Scholar]
  116. Buquicchio F.A. Understanding the Regulation of Residency and Exhaustion in CD8-Positive T Cells. Stanford University 2023
    [Google Scholar]
  117. Dunn G.P. Dunn I.F. Curry W.T. Focus on TILs: Prognostic significance of tumor infiltrating lymphocytes in human glioma. Cancer Immun. 2007 7 1 12 17691714
    [Google Scholar]
  118. Humeau J. Le Naour J. Galluzzi L. Kroemer G. Pol J.G. Trial watch: Intratumoral immunotherapy. OncoImmunology 2021 10 1 1984677 10.1080/2162402X.2021.1984677 34676147
    [Google Scholar]
  119. Smazynski J. Webb J.R. Resident memory-like tumor-infiltrating lymphocytes (TILRM): latest players in the immuno-oncology repertoire. Front. Immunol. 2018 9 1741 10.3389/fimmu.2018.01741 30093907
    [Google Scholar]
  120. Schön M.P. Arya A. Murphy E.A. Adams C.M. Strauch U.G. Agace W.W. Marsal J. Donohue J.P. Her H. Beier D.R. Olson S. Lefrancois L. Brenner M.B. Grusby M.J. Parker C.M. Mucosal T lymphocyte numbers are selectively reduced in integrin α E (CD103)-deficient mice. J. Immunol. 1999 162 11 6641 6649 10.4049/jimmunol.162.11.6641 10352281
    [Google Scholar]
  121. French J.J. Cresswell J. Wong W.K. Seymour K. Charnley R.M. Kirby J.A. T cell adhesion and cytolysis of pancreatic cancer cells: a role for E-cadherin in immunotherapy? Br. J. Cancer 2002 87 9 1034 1041 10.1038/sj.bjc.6600597 12434297
    [Google Scholar]
  122. Hossain M.A. Liu G. Dai B. Si Y. Yang Q. Wazir J. Birnbaumer L. Yang Y. Reinvigorating exhausted CD8 + cytotoxic T lymphocytes in the tumor microenvironment and current strategies in cancer immunotherapy. Med. Res. Rev. 2021 41 1 156 201 10.1002/med.21727 32844499
    [Google Scholar]
  123. Jin K. Yu Y. Zeng H. Liu Z. You R. Zhang H. Liu C. Su X. Yan S. Chang Y. Xu L. Xu J. Zhu Y. Wang Z. CD103+CD8+ tissue-resident memory T cell infiltration predicts clinical outcome and adjuvant therapeutic benefit in muscle-invasive bladder cancer. Br. J. Cancer 2022 126 11 1581 1588 10.1038/s41416‑022‑01725‑6 35165401
    [Google Scholar]
  124. Hoffmann J.C. Schön M.P. Integrin αE (CD103) β7 in epithelial cancer. Cancers 2021 13 24 6211 10.3390/cancers13246211 34944831
    [Google Scholar]
  125. Beumer-Chuwonpad A. Taggenbrock R.L.R.E. Ngo T.A. van Gisbergen K.P.J.M. The potential of tissue-resident memory T cells for adoptive immunotherapy against cancer. Cells 2021 10 9 2234 10.3390/cells10092234 34571883
    [Google Scholar]
  126. Raynor J.L. Chi H. Nutrients: Signal 4 in T cell immunity. J. Exp. Med. 2024 221 3 e20221839 10.1084/jem.20221839 38411744
    [Google Scholar]
  127. Li Y. Wan Y.Y. Zhu B. Immune cell metabolism in tumor microenvironment. Adv. Exp. Med. Biol. 2017 1011 163 196 10.1007/978‑94‑024‑1170‑6_5 28875490
    [Google Scholar]
  128. Giannone G. Ghisoni E. Genta S. Scotto G. Tuninetti V. Turinetto M. Valabrega G. Immuno-metabolism and microenvironment in cancer: key players for immunotherapy. Int. J. Mol. Sci. 2020 21 12 4414 10.3390/ijms21124414 32575899
    [Google Scholar]
  129. Williams J.B. Kupper T.S. Resident memory T cells in the tumor microenvironment. Tumor Microenvironment: Hematopoietic Cells–Part B 2020 39 68
    [Google Scholar]
  130. Van Acker H.H. Ma S. Scolaro T. Kaech S.M. Mazzone M. How metabolism bridles cytotoxic CD8+ T cells through epigenetic modifications. Trends Immunol. 2021 42 5 401 417 10.1016/j.it.2021.03.006 33867272
    [Google Scholar]
  131. Bystrom J. Taher T.E. Mageed R.A. Metabolic pathways underpinning lymphocyte differentiation and responses in health and disease. Immunometabolism (Cobham) 2020 2 3 e200024 10.20900/immunometab20200024
    [Google Scholar]
  132. Anadon C.M. Ovarian cancer immunogenicity is governed by a narrow subset of progenitor tissue-resident memory T cells. Cancer Cell 2022 40 5 545 557 10.1016/j.ccell.2022.03.008
    [Google Scholar]
  133. Liikanen I. Lauhan C. Quon S. Omilusik K. Phan A.T. Bartrolí L.B. Ferry A. Goulding J. Chen J. Scott-Browne J.P. Yustein J.T. Scharping N.E. Witherden D.A. Goldrath A.W. Hypoxia-inducible factor activity promotes antitumor effector function and tissue residency by CD8+ T cells. J. Clin. Invest. 2021 131 7 e143729 10.1172/JCI143729 33792560
    [Google Scholar]
  134. Singh V. Dwivedi S. Agrawal R. Ps M.R. Bansal A. Agarwal A. Misra S. Transporter Associated with Antigen Processing Proteins (TAP-1 and TAP-2) Gene Expression of MHC-I Downregulated in Oral Squamous Carcinoma. Endocr. Metab. Immune Disord. Drug Targets 2025 25 10.2174/0118715303344715241225184322 39950478
    [Google Scholar]
  135. Li J. Xiao C. Li C. He J. Tissue-resident immune cells: from defining characteristics to roles in diseases. Signal Transduct. Target. Ther. 2025 10 1 12 10.1038/s41392‑024‑02050‑5 39820040
    [Google Scholar]
  136. Yenyuwadee S. Sanchez-Trincado Lopez J.L. Shah R. Rosato P.C. Boussiotis V.A. The evolving role of tissue-resident memory T cells in infections and cancer. Sci. Adv. 2022 8 33 eabo5871 10.1126/sciadv.abo5871 35977028
    [Google Scholar]
  137. Winter S. The role of tissue-resident memory T cells in cutaneous metastatic melanoma. Murdoch University 2014
    [Google Scholar]
  138. Namuduri M. Brentjens R.J. Enhancing CAR T cell efficacy: the next step toward a clinical revolution? Expert Rev. Hematol. 2020 13 5 533 543 10.1080/17474086.2020.1753501 32267181
    [Google Scholar]
  139. Knochelmann H.M. Smith A.S. Dwyer C.J. Wyatt M.M. Mehrotra S. Paulos C.M. CAR T cells in solid tumors: Blueprints for building effective therapies. Front. Immunol. 2018 9 1740 10.3389/fimmu.2018.01740 30140266
    [Google Scholar]
  140. Li Y. Characterization and optimization of antigen-specific T cell responses during ex vivo expansion of melanoma tumor infiltrating lymphocytes. UT GSBS Dissertations and Theses 2010
    [Google Scholar]
  141. Leong J.W. Chase J.M. Romee R. Schneider S.E. Sullivan R.P. Cooper M.A. Fehniger T.A. Preactivation with IL-12, IL-15, and IL-18 induces CD25 and a functional high-affinity IL-2 receptor on human cytokine-induced memory-like natural killer cells. Biol. Blood Marrow Transplant. 2014 20 4 463 473 10.1016/j.bbmt.2014.01.006 24434782
    [Google Scholar]
  142. Qin V.M. D’Souza C. Neeson P.J. Zhu J.J. Chimeric antigen receptor beyond CAR-T cells. Cancers 2021 13 3 404 10.3390/cancers13030404 33499101
    [Google Scholar]
  143. Kim H. Shim B.Y. Lee S.J. Lee J.Y. Lee H.J. Kim I.H. Loss of von Hippel–Lindau (VHL) tumor suppressor gene function: VHL–HIF pathway and advances in treatments for metastatic renal cell carcinoma (RCC). Int. J. Mol. Sci. 2021 22 18 9795 10.3390/ijms22189795 34575959
    [Google Scholar]
  144. Reina-Campos M. Heeg M. Kennewick K. Mathews I.T. Galletti G. Luna V. Nguyen Q. Huang H. Milner J.J. Hu K.H. Vichaidit A. Santillano N. Boland B.S. Chang J.T. Jain M. Sharma S. Krummel M.F. Chi H. Bensinger S.J. Goldrath A.W. Metabolic programs of T cell tissue residency empower tumour immunity. Nature 2023 621 7977 179 187 10.1038/s41586‑023‑06483‑w 37648857
    [Google Scholar]
  145. Shin H. Iwasaki A. Tissue‐resident memory T cells. Immunol. Rev. 2013 255 1 165 181 10.1111/imr.12087 23947354
    [Google Scholar]
  146. Riley R.S. June C.H. Langer R. Mitchell M.J. Delivery technologies for cancer immunotherapy. Nat. Rev. Drug Discov. 2019 18 3 175 196 10.1038/s41573‑018‑0006‑z 30622344
    [Google Scholar]
  147. Coventry B.J. Therapeutic vaccination immunomodulation: forming the basis of all cancer immunotherapy. Ther. Adv. Vaccines Immunother. 2019 7 2515135519862234 10.1177/2515135519862234 31414074
    [Google Scholar]
  148. Xiao M. Xie L. Cao G. Lei S. Wang P. Wei Z. Luo Y. Fang J. Yang X. Huang Q. Xu L. Guo J. Wen S. Wang Z. Wu Q. Tang J. Wang L. Chen X. Chen C. Zhang Y. Yao W. Ye J. He R. Huang J. Ye L. CD4+ T-cell epitope-based heterologous prime-boost vaccination potentiates anti-tumor immunity and PD-1/PD-L1 immunotherapy. J. Immunother. Cancer 2022 10 5 e004022 10.1136/jitc‑2021‑004022 35580929
    [Google Scholar]
  149. Reschke R. Deitert B. Enk A.H. Hassel J.C. The role of tissue-resident memory T cells as mediators for response and toxicity in immunotherapy-treated melanoma—two sides of the same coin? Front. Immunol. 2024 15 1385781 10.3389/fimmu.2024.1385781 38562921
    [Google Scholar]
  150. Cao H. Huang T. Dai M. Kong X. Liu H. Zheng Z. Sun G. Sun G. Rong D. Jin Z. Tang W. Xia Y. Tumor microenvironment and its implications for antitumor immunity in cholangiocarcinoma: Future perspectives for novel therapies. Int. J. Biol. Sci. 2022 18 14 5369 5390 10.7150/ijbs.73949 36147461
    [Google Scholar]
  151. Wiggins B.G. Phenotypic and functional characterisation of CD4+ T cells in the human liver. University of Birmingham 2018
    [Google Scholar]
  152. Barnestein R. Galland L. Kalfeist L. Ghiringhelli F. Ladoire S. Limagne E. Immunosuppressive tumor microenvironment modulation by chemotherapies and targeted therapies to enhance immunotherapy effectiveness. OncoImmunology 2022 11 1 2120676 10.1080/2162402X.2022.2120676 36117524
    [Google Scholar]
  153. Gitto S. Natalini A. Antonangeli F. Di Rosa F. The emerging interplay between recirculating and tissue-resident memory T cells in cancer immunity: lessons learned from PD-1/PD-L1 blockade therapy and remaining gaps. Front. Immunol. 2021 12 755304 10.3389/fimmu.2021.755304 34867987
    [Google Scholar]
  154. Tang R. Wang H. Tang M. Roles of tissue-resident immune cells in immunotherapy of non-small cell lung cancer. Front. Immunol. 2023 14 1332814 10.3389/fimmu.2023.1332814 38130725
    [Google Scholar]
  155. Abdeljaoued S. Arfa S. Kroemer M. Ben Khelil M. Vienot A. Heyd B. Loyon R. Doussot A. Borg C. Tissue-resident memory T cells in gastrointestinal cancer immunology and immunotherapy: ready for prime time? J. Immunother. Cancer 2022 10 4 e003472 10.1136/jitc‑2021‑003472 35470231
    [Google Scholar]
/content/journals/mrmc/10.2174/0113895575412480251114071338
Loading
/content/journals/mrmc/10.2174/0113895575412480251114071338
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test