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      Tissue-resident exhausted and memory CD8+ T cells have distinct ontogeny, function and role in disease – Immunology Research


    • Christo, S. N., Park, S. L., Mueller, S. N. & Mackay, L. K. The multifaceted role of tissue-resident memory T cells. Annu. Rev. Immunol. 42, 317–345 (2024).

      Article 
      PubMed 

      Google Scholar
       

    • Szabo P. A., Miron M., Farber D. L. Location, location, location: tissue resident memory T cells in mice and humans. Sci Immunol. https://doi.org/10.1126/sciimmunol.aas9673 (2019).

    • Milner, J. J. et al. Runx3 programs CD8+ T cell residency in non-lymphoid tissues and tumours. Nature 552, 253–257 (2017).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Mackay, L. K. et al. Hobit and Blimp1 instruct a universal transcriptional program of tissue residency in lymphocytes. Science 352, 459–463 (2016).

      Article 
      PubMed 

      Google Scholar
       

    • Crowl, J. T. et al. Tissue-resident memory CD8(+) T cells possess unique transcriptional, epigenetic and functional adaptations to different tissue environments. Nat. Immunol. 23, 1121–1131 (2022).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Mackay, L. K. et al. The developmental pathway for CD103+CD8+ tissue-resident memory T cells of skin. Artic. Nat. Immunol. 14, 1294–1301 (2013).

      Article 

      Google Scholar
       

    • Gebhardt, T. et al. Memory T cells in nonlymphoid tissue that provide enhanced local immunity during infection with herpes simplex virus. Nat. Immunol. 10, 524–530 (2009).

      Article 
      PubMed 

      Google Scholar
       

    • Park, S. L. et al. Local proliferation maintains a stable pool of tissue-resident memory T cells after antiviral recall responses. Nat. Immunol. 19, 183–191 (2018).

      Article 
      PubMed 

      Google Scholar
       

    • Schenkel, J. et al. cell memory. Resident memory CD8 T cells trigger protective innate and adaptive immune responses. Science 346, 98–101 (2014).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Park, S. L. et al. Tissue-resident memory CD8+ T cells promote melanoma–immune equilibrium in skin. Nature 565, 366–371 (2019).

      Article 
      PubMed 

      Google Scholar
       

    • Wijeyesinghe, S. et al. Expansible residence decentralizes immune homeostasis. Nature 592, 457–462 (2021).

      Article 
      PubMed 

      Google Scholar
       

    • McLane L., Abdel-Hakeem M., Wherry E. CD8 T cell exhaustion during chronic viral infection and cancer. Annu. Rev. Immunol. https://doi.org/10.1146/annurev-immunol-041015-055318 (2019).

    • Sen, D. R. et al. The epigenetic landscape of T cell exhaustion. Science 354, 1165 (2016).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Pauken, K. E. et al. Epigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade. Science 354, 1160 (2016).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Khan, O. et al. TOX transcriptionally and epigenetically programs CD8+ T cell exhaustion. Nature 571, 211–218 (2019).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Alfei, F. et al. TOX reinforces the phenotype and longevity of exhausted T cells in chronic viral infection. Nature 571, 265–269 (2019).

      Article 
      PubMed 

      Google Scholar
       

    • Scott, A. C. et al. TOX is a critical regulator of tumour-specific T cell differentiation. Nature 571, 270–274 (2019).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Yao, C. et al. Single-cell RNA-seq reveals TOX as a key regulator of CD8(+) T cell persistence in chronic infection. Nat. Immunol. 20, 890–901 (2019).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Lan, X., Zebley, C. C. & Youngblood, B. Cellular and molecular waypoints along the path of T cell exhaustion. Sci. Immunol. 8, eadg3868 (2023).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Im, S. J. et al. Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy. Nature 537, 417–421 (2016).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Christo, S. N. et al. Discrete tissue microenvironments instruct diversity in resident memory T cell function and plasticity. Nat. Immunol. 22, 1140–1151 (2021).

      Article 
      PubMed 

      Google Scholar
       

    • Isaacs, J. F. et al. CD39 is expressed on functional effector and tissue-resident memory CD8+ T cells. J. Immunol. 213, 588–599 (2024).

      Article 
      PubMed 

      Google Scholar
       

    • Kurd N. S. et al. Early precursors and molecular determinants of tissue-resident memory CD8(+) T lymphocytes revealed by single-cell RNA sequencing. Sci. Immunol. https://doi.org/10.1126/sciimmunol.aaz6894 (2020).

    • Wherry, E. J., Blattman, J. N., Murali-Krishna, K., van der Most, R. & Ahmed, R. Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment. J. Virol. 77, 4911–4927 (2003).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Im, S. J., Konieczny, B. T., Hudson, W. H., Masopust, D. & Ahmed, R. PD-1+ stemlike CD8 T cells are resident in lymphoid tissues during persistent LCMV infection. Proc. Natl Acad. Sci. USA 117, 4292 (2020).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Beura, L. K. et al. Lymphocytic choriomeningitis virus persistence promotes effector-like memory differentiation and enhances mucosal T cell distribution. J. Leukoc. Biol. 97, 217–225 (2015).

      Article 
      PubMed 

      Google Scholar
       

    • Scott, M. C. et al. Deep profiling deconstructs features associated with memory CD8(+) T cell tissue residence. Immunity 58, 162–181.e10 (2025).

      Article 
      PubMed 

      Google Scholar
       

    • Beltra, J. C. et al. Developmental relationships of four exhausted CD8(+) T cell subsets reveals underlying transcriptional and epigenetic landscape control mechanisms. Immunity 52, 825–841.e8 (2020).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Gavil, N. V. et al. Chronic antigen in solid tumors drives a distinct program of T cell residence. Sci. Immunol. 8, eadd5976 (2023).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Boland, B. S. et al. Heterogeneity and clonal relationships of adaptive immune cells in ulcerative colitis revealed by single-cell analyses. Sci. Immunol. 5, eabb4432 (2020).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Ryan, G. E., Harris, J. E. & Richmond, J. M. Resident memory T cells in autoimmune skin diseases. Front. Immunol. 12, 652191 (2021).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Gavil, N. V., Cheng, K. & Masopust, D. Resident memory T cells and cancer. Immunity 57, 1734–1751 (2024).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Boddupalli, C. S. et al. Interlesional diversity of T cell receptors in melanoma with immune checkpoints enriched in tissue-resident memory T cells. JCI Insight 1, e88955 (2016).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Caushi, J. X. et al. Transcriptional programs of neoantigen-specific TIL in anti-PD-1-treated lung cancers. Nature 596, 126–132 (2021).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Banchereau R. et al. Intratumoral CD103+ CD8+ T cells predict response to PD-L1 blockade. J. Immunother. Cancer. https://doi.org/10.1136/jitc-2020-002231 (2021).

    • Duhen, T. et al. Co-expression of CD39 and CD103 identifies tumor-reactive CD8 T cells in human solid tumors. Nat. Commun. 9, 2724 (2018).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Simoni, Y. et al. Bystander CD8+ T cells are abundant and phenotypically distinct in human tumour infiltrates. Nature 557, 575–579 (2018).

      Article 
      PubMed 

      Google Scholar
       

    • 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. 19, 538–546 (2018).

      Article 
      PubMed 

      Google Scholar
       

    • Okła K., Farber D. L., Zou W. Tissue-resident memory T cells in tumor immunity and immunotherapy. J. Exp. Med. https://doi.org/10.1084/jem.20201605 (2021).

    • Luoma, A. M. et al. Tissue-resident memory and circulating T cells are early responders to pre-surgical cancer immunotherapy. Cell 185, 2918–2935.e29 (2022).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Savas, P. et al. Single-cell profiling of breast cancer T cells reveals a tissue-resident memory subset associated with improved prognosis. Nat. Med. 24, 986–993 (2018).

      Article 
      PubMed 

      Google Scholar
       

    • Clarke J. et al. Single-cell transcriptomic analysis of tissue-resident memory T cells in human lung cancer. J. Exp. Med. https://doi.org/10.1084/jem.20190249 (2019).

    • Corgnac S. et al. CD103+CD8+ TRM cells accumulate in tumors of anti-pd-1-responder lung cancer patients and are tumor-reactive lymphocytes enriched with Tc17. Cell Rep. Med. https://doi.org/10.1016/j.xcrm.2020.100127 (2020).

    • Masopust, D. et al. Dynamic T cell migration program provides resident memory within intestinal epithelium. J. Exp. Med. 207, 553–564 (2010).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Casey, K. A. et al. Antigen-independent differentiation and maintenance of effector-like resident memory T cells in tissues. J. Immunol. 188, 4866–4875 (2012).

      Article 
      PubMed 

      Google Scholar
       

    • Steinert, E. et al. Quantifying memory CD8+ T cells reveals regionalization of immunosurveillance. Cell 161, 737–749 (2015).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Zhang, N. & Bevan, M. J. Transforming growth factor-β signaling controls the formation and maintenance of gut-resident memory T cells by regulating migration and retention. Immunity 39, 687–696 (2013).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Macleod B. L. et al. A network of immune and microbial modifications underlies viral persistence in the gastrointestinal tract. J. Exp. Med. https://doi.org/10.1084/jem.20191473 (2020).

    • Sandu I. et al. Landscape of exhausted virus-specific CD8 T cells in chronic LCMV infection. Cell Rep. https://doi.org/10.1016/j.celrep.2020.108078 (2020).

    • Daniel, B. et al. Divergent clonal differentiation trajectories of T cell exhaustion. Nat. Immunol. 23, 1614–1627 (2022).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Ariotti, S. et al. Tissue-resident memory CD8+ T cells continuously patrol skin epithelia to quickly recognize local antigen. Proc. Natl Acad. Sci. USA 109, 19739–19744 (2012).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Schenkel J. M., Fraser K. A., Vezys V., Masopust D. Sensing and alarm function of resident memory CD8+ T cells. Nat Immunol. https://doi.org/10.1038/ni.2568 (2013).

    • Beura, L. K. et al. Intravital mucosal imaging of CD8+ resident memory T cells shows tissue-autonomous recall responses that amplify secondary memory. Nat. Immunol. 19, 173 (2018).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Behr, F. M. et al. Tissue-resident memory CD8+ T cells shape local and systemic secondary T cell responses. Nat. Immunol. 21, 1070–1081 (2020).

      Article 
      PubMed 

      Google Scholar
       

    • Fonseca, R. et al. Developmental plasticity allows outside-in immune responses by resident memory T cells. Nat. Immunol. 21, 412–421 (2020).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Swanson, E. et al. Simultaneous trimodal single-cell measurement of transcripts, epitopes, and chromatin accessibility using TEA-seq. eLife 10, e63632 (2021).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Buquicchio, F. A. et al. Distinct epigenomic landscapes underlie tissue-specific memory T cell differentiation. Immunity 57, 2202–2215.e6 (2024).

      Article 
      PubMed 

      Google Scholar
       

    • Wu, J. et al. T cell factor 1 suppresses CD103+ lung tissue-resident memory T cell development. Cell Rep. 31, 107484 (2020).

      Article 
      PubMed 

      Google Scholar
       

    • Fleck, J. S. et al. Inferring and perturbing cell fate regulomes in human brain organoids. Nature 621, 365–372 (2023).

      Article 
      PubMed 

      Google Scholar
       

    • Weber E. W. et al. Transient rest restores functionality in exhausted CAR-T cells through epigenetic remodeling. Science https://doi.org/10.1126/science.aba1786 (2021).

    • Schade, A. E. et al. Dasatinib, a small-molecule protein tyrosine kinase inhibitor, inhibits T-cell activation and proliferation. Blood 111, 1366–1377 (2008).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Wherry, E. J. et al. Molecular signature of CD8+ T cell exhaustion during chronic viral infection. Immunity 27, 670–684 (2007).

      Article 
      PubMed 

      Google Scholar
       

    • Giles, J. R. et al. Shared and distinct biological circuits in effector, memory and exhausted CD8+ T cells revealed by temporal single-cell transcriptomics and epigenetics. Nat. Immunol. 23, 1600–1613 (2022).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Zheng, L. et al. Pan-cancer single-cell landscape of tumor-infiltrating T cells. Science 374, abe6474 (2021).

      Article 
      PubMed 

      Google Scholar
       

    • Elmentaite, R. et al. Cells of the human intestinal tract mapped across space and time. Nature 597, 250–255 (2021).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Giles, J. R. et al. Human epigenetic and transcriptional T cell differentiation atlas for identifying functional T cell-specific enhancers. Immunity 55, 557–574.e7 (2022).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Stelekati, E. et al. Bystander chronic infection negatively impacts development of CD8(+) T cell memory. Immunity 40, 801–813 (2014).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Ge, C. et al. Bystander activation of pulmonary TRM cells attenuates the severity of bacterial pneumonia by enhancing neutrophil recruitment. Cell Rep. 29, 4236–4244.e3 (2019).

      Article 
      PubMed 

      Google Scholar
       

    • Sheridan, B. S. et al. Oral infection drives a distinct population of intestinal resident memory CD8+ T cells with enhanced protective function. Immunity 40, 747–757 (2014).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Park, S. L., Gebhardt, T. & Mackay, L. K. Tissue-resident memory T cells in cancer immunosurveillance. Trends Immunol. 40, 735–747 (2019).

      Article 
      PubMed 

      Google Scholar
       

    • Edwards, J. et al. CD103+ tumor-resident CD8+ T cells are associated with improved survival in immunotherapy-naive melanoma patients and expand significantly during anti-PD-1 treatment. Clin. Cancer Res. 24, 3036–3045 (2018).

      Article 
      PubMed 

      Google Scholar
       

    • Jaiswal, A. et al. An activation to memory differentiation trajectory of tumor-infiltrating lymphocytes informs metastatic melanoma outcomes. Cancer Cell 40, 524–544.e5 (2022).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Curtis, C. et al. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature 486, 346–352 (2012).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Liu, D. et al. Integrative molecular and clinical modeling of clinical outcomes to PD1 blockade in patients with metastatic melanoma. Nat. Med. 25, 1916–1927 (2019).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Matloubian, M. et al. Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature 427, 355–360 (2004).

      Article 
      PubMed 

      Google Scholar
       

    • Beura, L. K. et al. T cells in nonlymphoid tissues give rise to lymph-node-resident memory T cells. Immunity 48, 327–338 (2018).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Mackay, L. K. et al. Maintenance of T cell function in the face of chronic antigen stimulation and repeated reactivation for a latent virus infection. J. Immunol. 2012, 2173–2178 (2012).

      Article 

      Google Scholar
       

    • Zhu, J. et al. Immune surveillance by CD8αα+ skin-resident T cells in human herpes virus infection. Nature 497, 494–497 (2013).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Malik, B. T. et al. Resident memory T cells in the skin mediate durable immunity to melanoma. Sci. Immunol. 2, eaam6346 (2017).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Miller, B. C. et al. Subsets of exhausted CD8+ T cells differentially mediate tumor control and respond to checkpoint blockade. Nat. Immunol. 20, 326–336 (2019).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Minnie S. A., et al. TIM-3+ CD8 T cells with a terminally exhausted phenotype retain functional capacity in hematological malignancies. Sci. Immunol. https://doi.org/10.1126/sciimmunol.adg1094 (2024).

    • LaFleur, M. W. et al. PTPN2 regulates the generation of exhausted CD8(+) T cell subpopulations and restrains tumor immunity. Nat. Immunol. 20, 1335–1347 (2019).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Krishna, S. et al. Stem-like CD8 T cells mediate response of adoptive cell immunotherapy against human cancer. Science 370, 1328–1334 (2020).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Guo, Y. et al. Metabolic reprogramming of terminally exhausted CD8(+) T cells by IL-10 enhances anti-tumor immunity. Nat. Immunol. 22, 746–756 (2021).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Lee, Y. J. et al. CD39(+) tissue-resident memory CD8(+) T cells with a clonal overlap across compartments mediate antitumor immunity in breast cancer. Sci. Immunol. 7, eabn8390 (2022).

      Article 
      PubMed 

      Google Scholar
       

    • Virassamy, B. et al. Intratumoral CD8+ T cells with a tissue-resident memory phenotype mediate local immunity and immune checkpoint responses in breast cancer. Cancer Cell 41, 585–601.e8 (2023).

      Article 
      PubMed 

      Google Scholar
       

    • Blackburn, S. D., Shin, H., Freeman, G. J. & Wherry, E. J. Selective expansion of a subset of exhausted CD8 T cells by αPD-L1 blockade. Proc. Natl Acad. Sci. USA 105, 15016–15021 (2008).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Siddiqui, I. et al. Intratumoral Tcf1+ PD-1+ CD8+ T cells with stem-like properties promote tumor control in response to vaccination and checkpoint blockade immunotherapy. Immunity 50, 195–211 (2019).

      Article 
      PubMed 

      Google Scholar
       

    • Voabil, P. et al. An ex vivo tumor fragment platform to dissect response to PD-1 blockade in cancer. Nat. Med. 27, 1250–1261 (2021).

      Article 
      PubMed 

      Google Scholar
       

    • Odorizzi, P. M., Pauken, K. E., Paley, M. A., Sharpe, A. & Wherry, E. J. Genetic absence of PD-1 promotes accumulation of terminally differentiated exhausted CD8+ T cells. J. Exp. Med. 212, 1125–1137 (2015).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Anderson, K. G. et al. Intravascular staining for discrimination of vascular and tissue leukocytes. Nat. Protoc. 9, 209–222 (2014).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • O’Flanagan, C. H. et al. Dissociation of solid tumor tissues with cold active protease for single-cell RNA-seq minimizes conserved collagenase-associated stress responses. Genome Biol. 20, 210 (2019).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Abascal, F. et al. Expanded encyclopaedias of DNA elements in the human and mouse genomes. Nature 583, 699–710 (2020).

      Article 

      Google Scholar
       

    • Siepel, A. et al. Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Res. 15, 1034–1050 (2005).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Kartha, V. K. et al. Functional inference of gene regulation using single-cell multi-omics. Cell Genom. 2, 100166 (2022).

      Article 
      PubMed 
      PubMed Central 

      Google Scholar
       

    • Rauluseviciute, I. et al. JASPAR 2024: 20th anniversary of the open-access database of transcription factor binding profiles. Nucleic Acids Res. 52, D174–D182 (2024).

      Article 
      PubMed 

      Google Scholar
       

    • Shen, W.-K. et al. AnimalTFDB 4.0: a comprehensive animal transcription factor database updated with variation and expression annotations. Nucleic Acids Res. 51, D39–D45 (2023).

      Article 
      PubMed 

      Google Scholar
       

    • Nüssing S. et al. Efficient CRISPR/Cas9 gene editing in uncultured naive mouse T cells for in vivo studies. J. Immunol. https://doi.org/10.4049/jimmunol.1901396 (2020).



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