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).
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).
Mackay, L. K. et al. Hobit and Blimp1 instruct a universal transcriptional program of tissue residency in lymphocytes. Science 352, 459–463 (2016).
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).
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).
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).
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).
Schenkel, J. et al. cell memory. Resident memory CD8 T cells trigger protective innate and adaptive immune responses. Science 346, 98–101 (2014).
Park, S. L. et al. Tissue-resident memory CD8+ T cells promote melanoma–immune equilibrium in skin. Nature 565, 366–371 (2019).
Wijeyesinghe, S. et al. Expansible residence decentralizes immune homeostasis. Nature 592, 457–462 (2021).
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).
Pauken, K. E. et al. Epigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade. Science 354, 1160 (2016).
Khan, O. et al. TOX transcriptionally and epigenetically programs CD8+ T cell exhaustion. Nature 571, 211–218 (2019).
Alfei, F. et al. TOX reinforces the phenotype and longevity of exhausted T cells in chronic viral infection. Nature 571, 265–269 (2019).
Scott, A. C. et al. TOX is a critical regulator of tumour-specific T cell differentiation. Nature 571, 270–274 (2019).
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).
Lan, X., Zebley, C. C. & Youngblood, B. Cellular and molecular waypoints along the path of T cell exhaustion. Sci. Immunol. 8, eadg3868 (2023).
Im, S. J. et al. Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy. Nature 537, 417–421 (2016).
Christo, S. N. et al. Discrete tissue microenvironments instruct diversity in resident memory T cell function and plasticity. Nat. Immunol. 22, 1140–1151 (2021).
Isaacs, J. F. et al. CD39 is expressed on functional effector and tissue-resident memory CD8+ T cells. J. Immunol. 213, 588–599 (2024).
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).
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).
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).
Scott, M. C. et al. Deep profiling deconstructs features associated with memory CD8(+) T cell tissue residence. Immunity 58, 162–181.e10 (2025).
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).
Gavil, N. V. et al. Chronic antigen in solid tumors drives a distinct program of T cell residence. Sci. Immunol. 8, eadd5976 (2023).
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).
Ryan, G. E., Harris, J. E. & Richmond, J. M. Resident memory T cells in autoimmune skin diseases. Front. Immunol. 12, 652191 (2021).
Gavil, N. V., Cheng, K. & Masopust, D. Resident memory T cells and cancer. Immunity 57, 1734–1751 (2024).
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).
Caushi, J. X. et al. Transcriptional programs of neoantigen-specific TIL in anti-PD-1-treated lung cancers. Nature 596, 126–132 (2021).
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).
Simoni, Y. et al. Bystander CD8+ T cells are abundant and phenotypically distinct in human tumour infiltrates. Nature 557, 575–579 (2018).
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).
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).
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).
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).
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).
Steinert, E. et al. Quantifying memory CD8+ T cells reveals regionalization of immunosurveillance. Cell 161, 737–749 (2015).
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).
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).
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).
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).
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).
Fonseca, R. et al. Developmental plasticity allows outside-in immune responses by resident memory T cells. Nat. Immunol. 21, 412–421 (2020).
Swanson, E. et al. Simultaneous trimodal single-cell measurement of transcripts, epitopes, and chromatin accessibility using TEA-seq. eLife 10, e63632 (2021).
Buquicchio, F. A. et al. Distinct epigenomic landscapes underlie tissue-specific memory T cell differentiation. Immunity 57, 2202–2215.e6 (2024).
Wu, J. et al. T cell factor 1 suppresses CD103+ lung tissue-resident memory T cell development. Cell Rep. 31, 107484 (2020).
Fleck, J. S. et al. Inferring and perturbing cell fate regulomes in human brain organoids. Nature 621, 365–372 (2023).
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).
Wherry, E. J. et al. Molecular signature of CD8+ T cell exhaustion during chronic viral infection. Immunity 27, 670–684 (2007).
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).
Zheng, L. et al. Pan-cancer single-cell landscape of tumor-infiltrating T cells. Science 374, abe6474 (2021).
Elmentaite, R. et al. Cells of the human intestinal tract mapped across space and time. Nature 597, 250–255 (2021).
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).
Stelekati, E. et al. Bystander chronic infection negatively impacts development of CD8(+) T cell memory. Immunity 40, 801–813 (2014).
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).
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).
Park, S. L., Gebhardt, T. & Mackay, L. K. Tissue-resident memory T cells in cancer immunosurveillance. Trends Immunol. 40, 735–747 (2019).
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).
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).
Curtis, C. et al. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature 486, 346–352 (2012).
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).
Matloubian, M. et al. Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature 427, 355–360 (2004).
Beura, L. K. et al. T cells in nonlymphoid tissues give rise to lymph-node-resident memory T cells. Immunity 48, 327–338 (2018).
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).
Zhu, J. et al. Immune surveillance by CD8αα+ skin-resident T cells in human herpes virus infection. Nature 497, 494–497 (2013).
Malik, B. T. et al. Resident memory T cells in the skin mediate durable immunity to melanoma. Sci. Immunol. 2, eaam6346 (2017).
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).
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).
Krishna, S. et al. Stem-like CD8 T cells mediate response of adoptive cell immunotherapy against human cancer. Science 370, 1328–1334 (2020).
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).
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).
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).
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).
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).
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).
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).
Anderson, K. G. et al. Intravascular staining for discrimination of vascular and tissue leukocytes. Nat. Protoc. 9, 209–222 (2014).
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).
Abascal, F. et al. Expanded encyclopaedias of DNA elements in the human and mouse genomes. Nature 583, 699–710 (2020).
Siepel, A. et al. Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Res. 15, 1034–1050 (2005).
Kartha, V. K. et al. Functional inference of gene regulation using single-cell multi-omics. Cell Genom. 2, 100166 (2022).
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).
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).
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).
Read more about this post…
Credits: Source
Disclaimer




Serving