Cited by 934Cancer Immunotherapy and BiomarkersT-cell and B-cell ImmunologyImmunotherapy and Immune Responses

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Chromatin states define tumour-specific T cell dysfunction and reprogramming

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Philip, Mary, Fairchild, Lauren, Sun, Liping, Horste, Ellen L., Camara, Steven, Shakiba, Mojdeh, Scott, Andrew C., Viale, Agnes, Lauer, Peter, Merghoub, Taha, Hellmann, Matthew D., Wolchok, Jedd D., Leslie, Christina S., Schietinger, Andrea·2017·Nature

DOI 10.1038/nature22367PMC PMC5693219

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Abstract

Tumour-specific CD8 T cells in solid tumours are dysfunctional, allowing tumours to progress. The epigenetic regulation of T cell dysfunction and therapeutic reprogrammability (for example, to immune checkpoint blockade) is not well understood. Here we show that T cells in mouse tumours differentiate through two discrete chromatin states: a plastic dysfunctional state from which T cells can be rescued, and a fixed dysfunctional state in which the cells are resistant to reprogramming. We identified surface markers associated with each chromatin state that distinguished reprogrammable from non-reprogrammable PD1 hi dysfunctional T cells within heterogeneous T cell populations from tumours in mice; these surface markers were also expressed on human PD1 hi tumour-infiltrating CD8 T cells. Our study has important implications for cancer immunotherapy as we define key transcription factors and epigenetic programs underlying T cell dysfunction and surface markers that predict therapeutic reprogrammability.

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Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106
Fast gapped-read alignment with Bowtie 2
Langmead, B., & Salzberg, S. L. (2012) · Nature Methods · doi:10.1038/nmeth.1923 · Cited by 56,400
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989
BEDTools: a flexible suite of utilities for comparing genomic features
Quinlan, A. R., & Hall, I. M. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq033 · Cited by 27,437
Model-based Analysis of ChIP-Seq (MACS)
Zhang, Y., Liu, T., Meyer, C. A., Eeckhoute, J., Johnson, D. S., Bernstein, B. E., Nusbaum, C., Myers, R. M., Brown, M., Li, W., et al. (2008) · Genome Biology · doi:10.1186/gb-2008-9-9-r137 · Cited by 18,386
Differential expression analysis for sequence count data
Anders, S., & Huber, W. (2010) · Genome Biology · doi:10.1186/gb-2010-11-10-r106 · Cited by 15,581
Integrative genomics viewer
Robinson, J. T., Thorvaldsdóttir, H., Winckler, W., Guttman, M., Lander, E. S., Getz, G., & Mesirov, J. P. (2011) · Nature Biotechnology · doi:10.1038/nbt.1754 · Cited by 15,390
MEME SUITE: tools for motif discovery and searching
Bailey, T. L., Boden, M., Buske, F. A., Frith, M., Grant, C. E., Clementi, L., Ren, J., Li, W. W., & Noble, W. S. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp335 · Cited by 10,648
Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer
Rizvi, N. A., Hellmann, M. D., Snyder, A., Kvistborg, P., Makarov, V., Havel, J. J., Lee, W., Yuan, J., Wong, P., Ho, T. S., et al. (2015) · Science · doi:10.1126/science.aaa1348 · Cited by 7,802
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“These differences could be due to the differences between microenvironments in viral infection and in tumors [14].”
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“, for CD8 naïve, CD8 Effector memory, and CD8 Central Memory T cells) [21].”
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“Metabolic microenviroment glutamine Methylation Colorectal Cancer [47]”
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Shukla, S., Kumari, S., Bal, S. K., Mónaco, D. C., Ribeiro, S. P., Sékaly, R., & Sharma, A. (2021) · Current Opinion in HIV and AIDS · doi:10.1097/coh.0000000000000692 · Cited by 17
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Kotter, B., Engert, F., Krueger, W. H., Roy, A. J., Rawashdeh, W. A., Cordes, N., Drees, B., Webster, B., Werchau, N., Lock, D., et al. (2021) · Cancers · doi:10.3390/cancers13194741 · Cited by 17
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Youn, A., Márquez, E. J., Lawlor, N. T., Stitzel, M. L., & Ucar, D. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky1117 · Cited by 17
Personal tumor antigens in blood malignancies: genomics-directed identification and targeting
Penter, L., & Wu, C. J. (2020) · Journal of Clinical Investigation · doi:10.1172/jci129209 · Cited by 17
“The recent breathtaking technological advances have opened doors for a systematic understanding of target antigens (46, 50, 58), the identities and characteristics of subpopulations of TILs (160–162), and immunological aspects of disease biology (163).”
Background
Autoregulated splicing of TRA2 β programs T cell fate in response to antigen-receptor stimulation
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“Furthermore, the PEs of Srsf7 and Tra2 b were both differentially skipped in effector CD8 + T cells in RNA-seq data analyzed from mice with acute Listeria infectionat day 5 ( 19 ) but were reincluded in day 7 effector and memory CD8 + T cells (Fig.”
Background
Deciphering the role of histone modifications in memory and exhausted CD8 T cells
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“Multiple recent studies have used ATAC-seq to examine the unique chromatin accessibility landscape of T EX and to investigate how this landscape impacts T EX biology 5,6,8,10,7,9,112,113 .”
USP14-mediated metabolic competition impairs CD8+ T cell immunosurveillance in hepatocellular carcinoma
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“reported in 2017 that tumor-specific CD8 T lymphocytes acquire distinct dysfunction-related chromatin accessibility states throughout their time within the tumor, and in human CD8 T cells a chronic infection-induced epigenetic scarring was observed, which persisted long after the infection was resolved (124, 125).”
Background
The impact of Foxp3 + regulatory T‐cells on CD8 + T‐cell dysfunction in tumour microenvironments and responses to immune checkpoint inhibitors
Attias, M., & Piccirillo, C. A. (2024) · British Journal of Pharmacology · doi:10.1111/bph.16313 · Cited by 17
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Background
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“CrePR1) [33], a R26StopFLP110* conditional allele that carries a loxP-flanked Neo-STOP cassette preceding a constitutively active PIK3CA allele (encoding p110α protein) targeted to the Gt(ROSA)26Sor locus [34], and a conditional TP53 gene knockout [35].”
Background
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Barili, V., Vecchi, A. L., Rossi, M., Montali, I., Tiezzi, C., Penna, A., Laccabue, D., Missale, G., Fisicaro, P., & Boni, C. (2021) · Cells · doi:10.3390/cells10102563 · Cited by 18
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Background
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Background
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Background
Genetic and functional data identifying Cd101 as a type 1 diabetes (T1D) susceptibility gene in nonobese diabetic (NOD) mice
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“In particular, CD8-positive T cells might be interesting to study further since recent reports claimed altered functions between CD101-expressing CD8-positive T lymphocytes and their CD101-negative counterparts [55, 56].”
Background
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Background
Boosting engineered T cells
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Conservation and divergence in gene regulation between mouse and human immune cells deserves equal emphasis
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Background
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Background
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Background
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Background
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“22,23 The role of CD38 in human CAR T cells speci ﬁ cally is less well de ﬁ ned.”
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Shvefel, S. C., Pai, J. A., Cao, Y., Pal, L. R., Bartok, O., Levy, R., Zemanek, M. J., Weller, C., Herzog, E., Yao, W., et al. (2024) · Cancer Discovery · doi:10.1158/2159-8290.cd-23-1422 · Cited by 19
“A T cell exhaustion signature (a plastic dysfunctional state from which T cells can be rescued) of 25 genes from Philip and colleagues (104) was used to score the exhaustion of individual CD8 + T cells in each clone.”
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Self-citation
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“ChIP-quantitative PCR (qPCR) using primers targeting enriched promoter regions (Primer 1 and Primer 2) demonstrated that TRIM28 knockdown significantly reduced p65 occupancy at the PD-L1 promoter.”
Influential
Transcriptional regulator SATB1 limits CD8+ T cell population expansion and effector differentiation in chronic infection and cancer
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“Indeed, T EX cells in both chronic viral infection and tumors exhibit a unique epigenetic signature compared to naive, effector or memory T cells 22,32,33 .”
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Self-citation
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“Philip and colleagues (21) used ATAC-seq to study the epigenetic landscape of CD8þ TILs and identified two distinct CD8þ T-cell states in a murine tumor model— one that can be reversed upon in vitro activation and one that cannot.”
Method
The transferrin receptor CD71 regulates type II CD38, revealing tight topological compartmentalization of intracellular cyclic ADP-ribose production
Deng, Q. W., Zhang, J., Li, T., He, W., Fang, L., Lee, H. C., & Zhao, Y. J. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.010010 · Cited by 13
“It regulates various physiopathological processes, including insulin secretion (1), HIV infection (2), malignancies like leukemia (3) and myeloma (4), as well as dysfunction of tumorinfiltrating CD8 T cells (5).”
Background
Microbes as Master Immunomodulators: Immunopathology, Cancer and Personalized Immunotherapies
Lérias, J. R., Paraschoudi, G., de Sousa, E., Martins, J. D., Condeço, C., Figueiredo, N., Carvalho, C. T., Dodoo, E., Castillo-Martín, M., Antonio Lopez-beltran, B., et al. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00362 · Cited by 14
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Zhang, Y., & Liu, Z. (2025) · Advanced Science · doi:10.1002/advs.202508692 · Cited by 13
Functional and molecular characterization of PD1+ tumor-infiltrating lymphocytes from lung cancer patients.
Lipp, J., Wang, L., Yang, H., Yao, F., Harrer, N. E., Müller, S. J., Berezowska, S., Dorn, P., Marti, T. M., Schmid, R. A., et al. (2022) · BORIS (University Library Bern) · doi:10.48350/165815 · Cited by 12
Egress of resident memory T cells from tissue with neoadjuvant immunotherapy: Implications for systemic anti-tumor immunity
Rainey, M. A., Allen, C. T., & Craveiro, M. (2023) · Oral Oncology · doi:10.1016/j.oraloncology.2023.106570 · Cited by 12
Barriers to T Cell Functionality in the Glioblastoma Microenvironment
Nader, N. E., Frederico, S. C., Miller, T. A., Huq, S., Zhang, X., Kohanbash, G., & Hadjipanayis, C. G. (2024) · Cancers · doi:10.3390/cancers16193273 · Cited by 13
“In a murine model of liver cancer, CD8 T cells displayed unique chromatin remodeling (a form of epigenetic modification) specific to early exhaustion, or functional states, mainly within genomic regions of TCR signaling and cytokine production [38].”
Background
Unraveling the tumor microenvironment of esophageal squamous cell carcinoma through single-cell sequencing: A comprehensive review
Qi, L., Wang, J., Hou, S., Liu, S., Zhang, Q., Zhu, S., Liu, S., & Zhang, S. (2025) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2025.189264 · Cited by 15
Limitations of CAR-T-Cell Therapy in Hematologic Malignancies: Focusing on Antigen Escape and T-Cell Dysfunction
Lin, Y., Luo, S., Wei, J., Lin, S., Wang, D., Zhao, X., Feng, Z., Shen, Y., & Chen, Q. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26199669 · Cited by 12
“Clinical evidence suggests that combinatorial use of immune checkpoint inhibitors (e.g., anti-PD-1, anti-TIM3 antibodies) can partially reverse CAR-T-cell exhaustion and enhance antitumor activity [92,105–107].”
Modulation of Determinant Factors to Improve Therapeutic Combinations with Immune Checkpoint Inhibitors
Dosset, M., Joseph, E. L. M., Vargas, T. R., & Apétoh, L. (2020) · Cells · doi:10.3390/cells9071727 · Cited by 12
“A progressive strong expression of immune checkpoint receptors and fixed epigenetic alterations eventually lead to a steady-state inhibition of effector T cells, which cannot be further abrogated by ICPi therapy [11,71,123].”
Background
CD8+ T cell self-tolerance permits responsiveness but limits tissue damage
Truckenbrod, E. N., Burrack, K. S., Knutson, T. P., da Silva, H. B., Block, K. E., O’Flanagan, S. D., Stagliano, K. R., Hurwitz, A. A., Fulton, R. B., Renkema, K. R., et al. (2021) · eLife · doi:10.7554/elife.65615 · Cited by 13
“Recent studies on dysfunctional tumor-specific or exhausted CD8 T cells have shown that epigenetic changes in chromatin accessibility or methylation can maintain such states (Ghoneim et al., 2017; Pauken et al., 2016; Philip et al., 2017), which is one potential explanation for the cell-intrinsic nature of the toleran…”
Background
Solid Tumor Microenvironment Can Harbor and Support Functional Properties of Memory T Cells
Sullivan, P. M., Reed, S. J., Kalia, V., & Sarkar, S. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.706150 · Cited by 13
“Our findings that tumor infiltrating bystander CD8 T cells do not exhibit hallmarks of exhaustion, such as sustained inhibitory receptor expression, loss of cytokine production (4) and terminal differentiation (59), bear implications for future exploitation of bystander tumorresident memory T cells for indirect augmen…”
Background
Stem-like T cells and niches: Implications in human health and disease
Yi, L., & Li, Y. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.907172 · Cited by 15
Immune cell profiling in the age of immune checkpoint inhibitors: implications for biomarker discovery and understanding of resistance mechanisms
Lim, S. Y., & Rizos, H. (2018) · Mammalian Genome · doi:10.1007/s00335-018-9757-4 · Cited by 12
A Peptide-Based PD1 Antagonist Enhances T-Cell Priming and Efficacy of a Prophylactic Malaria Vaccine and Promotes Survival in a Lethal Malaria Model
Phares, T., Kotraiah, V., Karunarathne, D. S., Huang, J., Browne, C. D., Buontempo, P., Mansour, M., Noe, A., Wykes, M., Pannucci, J., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01377 · Cited by 10
Gene-regulatory network analysis of ankylosing spondylitis with a single-cell chromatin accessible assay
Yu, H., Wu, H., Zheng, F., Zhu, C., Yin, L., Dai, W., Liu, D. J., Tang, D., Hong, X., & Dai, Y. (2020) · Scientific Reports · doi:10.1038/s41598-020-76574-5 · Cited by 12
Imaging and AI based chromatin biomarkers for diagnosis and therapy evaluation from liquid biopsies
Challa, K., Paysan, D., Leiser, D., Sauder, N., Weber, D. C., & Shivashankar, G. V. (2023) · npj Precision Oncology · doi:10.1038/s41698-023-00484-8 · Cited by 11
“Consequently, liquid biopsies assessing the DNA methylation, miRNA, transcriptional and proteomic pro ﬁ les of blood cells (e.g. PBMCs), as well as alterations of their speci ﬁ c subpopulations, have become an active area of research 13,20,35,36 .”
Advances in macrophage and T cell metabolic reprogramming and immunotherapy in the tumor microenvironment
Cheng, H., & Zheng, Y. (2024) · PeerJ · doi:10.7717/peerj.16825 · Cited by 13
Lipids guide T cell antitumor immunity by shaping their metabolic and functional fitness
Rumiano, L., & Manzo, T. (2024) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2024.11.014 · Cited by 12
Tumor-specific CD8 + T cells from the bone marrow resist exhaustion and exhibit increased persistence in tumor-bearing hosts as compared with tumor-infiltrating lymphocytes
Zawidzka, E. M., Biavati, L., Thomas, A. M., Zanettini, C., Marchionni, L., Leone, R. D., & Borrello, I. (2025) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2024-009367 · Cited by 11
“44 45 Moreover, truly exhausted T cells are resistant to reprogramming.”
CircRNA GRAMD4 induces NBR1 expression to promote autophagy and immune escape in renal cell carcinoma
Zhou, M., Chen, M., Zheng, Z., Li, Q., Liao, L., Wang, Y., Xu, Y., Shu, G., Luo, J., Yang, T., et al. (2025) · Autophagy · doi:10.1080/15548627.2025.2503560 · Cited by 12
“While anti-PDCD1 therapy can restore T cells with early functional impairment, it may prove ineffective for T cells with severe functional deficits [41,42].”
Mechanisms of primary and acquired resistance to PD-1/PD-L1 blockade and the emerging role of gut microbiome
Zou, R., Wang, Y., Ye, F., Zhang, X., Wang, M., & Cui, S. (2021) · Clinical & Translational Oncology · doi:10.1007/s12094-021-02637-2 · Cited by 11
“While initially plastic and able to be modified to restore an effector functionality, they eventually reach a state of fixed epigenetic dysfunction, in which their chromatin is rendered inaccessible and resistant to further remodeling and reinvigoration [93].”
Background
Cutting Edge: Promoting T Cell Factor 1+ T Cell Self-Renewal to Improve Programmed Cell Death Protein 1 Blockade
Wang, P. H., Washburn, R. S., Maniar, R., Mu, M., Ringham, O. R., Kratchmarov, R., Henick, B. S., & Reiner, S. L. (2022) · The Journal of Immunology · doi:10.4049/jimmunol.2200317 · Cited by 11
Deep Learning Implicitly Handles Tissue Specific Phenomena to Predict Tumor DNA Accessibility and Immune Activity
Wnuk, K., Sudol, J., Givechian, K. B., Soon‐Shiong, P., Rabizadeh, S., Szeto, C. W., & Vaske, C. J. (2019) · iScience · doi:10.1016/j.isci.2019.09.018 · Cited by 10
Markers of immune activation: novel biomarkers to predict the early-warning indicator of patients with papillary thyroid carcinoma
Lu, H., Zhang, L., Dai, Y., Ruan, Y., Cao, X., Cai, X., Ruan, S., & Chen, Q. (2020) · Diagnostic Pathology · doi:10.1186/s13000-020-00931-1 · Cited by 11
Remodeling the chromatin landscape in T lymphocytes by a division of labor among transcription factors
Vahedi, G. (2021) · Immunological Reviews · doi:10.1111/imr.12942 · Cited by 11
Archetypes of checkpoint-responsive immunity
Im, K. W., Combes, A. J., Spitzer, M. H., Satpathy, A. T., & Krummel, M. F. (2021) · Trends in Immunology · doi:10.1016/j.it.2021.09.007 · Cited by 13
mTOR activation in CD8+ cells contributes to disease activity of rheumatoid arthritis and increases therapeutic response to TNF inhibitors
Zhang, M., Iwata, S., Sonomoto, K., Ueno, M., Fujita, Y., Anan, J., Miyazaki, Y., Ohkubo, N., Hajime, M., Todoroki, Y., et al. (2021) · Rheumatology · doi:10.1093/rheumatology/keab834 · Cited by 11
Histone Deacetylase Inhibitors Promote Latent Adenovirus Reactivation from Tonsillectomy Specimens
Wang, L., Zhang, M., Li, J., Yang, G., Huang, Q., Li, J., Wang, H., He, S., & Li, E. (2020) · Journal of Virology · doi:10.1128/jvi.00100-20 · Cited by 11
Dynamic single-cell systemic immune responses in immunotherapy-treated early-stage HR+ breast cancer patients
Sun, X., Axelrod, M. L., Waks, A. G., Fu, J., DiLullo, M. K., Allen, E. M. V., Tolaney, S. M., Mittendorf, E. A., Xu, Y., & Balko, J. M. (2025) · npj Breast Cancer · doi:10.1038/s41523-025-00776-1 · Cited by 10
Flt3L-mediated tumor cDC1 expansion enhances immunotherapy by priming stem-like CD8+ T cells in lymph nodes
Lai, J., Chan, C. W., Armitage, J. D., Audsley, K. M., Huang, Y., Derrick, E. B., Carstensen, L. S., Scheffler, C. M., Jones, M. E., Sek, K., et al. (2026) · Nature Immunology · doi:10.1038/s41590-026-02419-4 · Cited by 10
“The presence of T PEX , characterized by expression of TCF1 and a distinct transcriptional and epigenetic state relative to terminally exhausted T cells (T EX ), are crucial for antitumor immune responses following ICB, eliciting a proliferative burst post-therapy 3,9–13 .”
Investigating cellular similarities and differences between upper tract urothelial carcinoma and bladder urothelial carcinoma using single-cell sequencing
Zhang, Q., Wang, C., Qin, M., Ye, Y., Mo, Y., Meng, Q., Guanglin, Y., Feng, G., Lin, R., Xian, S., et al. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1298087 · Cited by 10
BRD4 inhibitor reduces exhaustion and blocks terminal differentiation in CAR-T cells by modulating BATF and EGR1
Sui, S., Zhong, M., Zhong, S., Peng, X., Mao, L., Chen, C., Zeng, C., Luo, O. J., & Li, Y. (2024) · Biomarker Research · doi:10.1186/s40364-024-00667-w · Cited by 12
“An early study has reported that T cell exhaustion involves two distinct chromatin states: a reversible dysfunctional state from which T cells can be rejuve-nated and an irreversible dysfunctional state in which T cells are recalcitrant to therapeutic reprogramming [19].”
Background
Functional subsets of tumor-specific CD8+ T cells in draining lymph nodes and tumor microenvironment
Huang, Q., Xu, L., & Ye, L. (2024) · Current Opinion in Immunology · doi:10.1016/j.coi.2024.102506 · Cited by 11
Anti-PD-1 amplifies costimulation in melanoma-infiltrating Th1-like Foxp3+ regulatory T cells to alleviate local immunosuppression
Attias, M., Alvarez, F., Al-Aubodah, T.-A., Istomine, R., McCallum, P. A., Huang, F., Sleiman, A., Nishimura, T., Rincon, S. V. D., Riazalhosseini, Y., et al. (2025) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2024-009435 · Cited by 12
“24 38 Nonetheless, T reg TILs are highly functional in TMEs 5 14 39 and it is unclear if they undergo exhaustion.”
Bacterial vaginosis associates with dysfunctional T cells and altered soluble immune factors in the cervicovaginal tract
MacLean, F., Tsegaye, A. T., Graham, J. B., Swarts, J. L., Vick, S. C., Potchen, N. B., Talavera, I. C., Warrier, L., Dubrulle, J., Schroeder, L. K., et al. (2025) · Journal of Clinical Investigation · doi:10.1172/jci184609 · Cited by 14
“Additionally, CD101 is associated with exhausted T cell phenotypes that result from chronic activation and can promote immune dysfunction (71–73).”
Self‐Promoting Targeted Delivery of Epigenetic Immunostimulants to Activate Breast Cancer Immunity via HDACs Downregulation and PD‐L1 Upregulation
Chen, X., Lu, L., Liang, Z., Yu, B., Shao, Z., Li, J., Cen, Y., Liu, Y., Li, S., & Chen, X. S. (2025) · Angewandte Chemie International Edition · doi:10.1002/anie.202502120 · Cited by 10
Integrated peripheral blood multi-omics profiling identifies immune signatures predictive of neoadjuvant PD-1 blockade efficacy in head and neck squamous cell carcinoma
Zhang, H., Wu, W., Wang, M., Zhang, J., Guo, C., Han, G., & Wang, L. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-06770-2 · Cited by 14
“Conversely, despite high cytotoxic potential (Perforin + , Granzyme B + ), the functionality of Temra cells is restricted by a terminal exhaustion phenotype (PD-1 high TIM-3 high ) and irreversible epigenetic modifications such as DNA methylation [43].”
Faithful modeling of terminal CD8+T cell dysfunction and epigenetic stabilization in vitro
Yousif, A., Saadey, A. A., Lowin, A. M., Yousif, A. M., Saini, A., Allison, M. R., Ptak, K., Oltz, E. M., & Ghoneim, H. E. (2025) · JCI Insight · doi:10.1172/jci.insight.191220 · Cited by 12
“Furthermore, it remains unclear whether in vitro–induced dysfunction is stable after antigen withdrawal — a core defining feature of the epigenetically fixed state of terminal exhaustion observed in vivo (11, 22–24).”
Multiple Myeloma, Targeting B-Cell Maturation Antigen With Chimeric Antigen Receptor T-Cells
Shah, U. A., & Smith, E. L. (2019) · The Cancer Journal · doi:10.1097/ppo.0000000000000379 · Cited by 11
Origin and fine-tuning of effector CD8 T cell subpopulations in chronic infection
Kanev, K., & Zehn, D. (2020) · Current Opinion in Virology · doi:10.1016/j.coviro.2020.10.003 · Cited by 10
Glycolytic expression in lower-grade glioma reveals an epigenetic association between IDH mutation status and PDL1/2 expression
Givechian, K. B., Garner, C. P., Benz, S. C., Rabizadeh, S., & Soon‐Shiong, P. (2020) · Neuro-Oncology Advances · doi:10.1093/noajnl/vdaa162 · Cited by 10
Transcriptome Analysis of Tumor-Infiltrating Lymphocytes Identifies NK Cell Gene Signatures Associated With Lymphocyte Infiltration and Survival in Soft Tissue Sarcomas
Judge, S. J., Bloomstein, J. D., Sholevar, C. J., Darrow, M. A., Stoffel, K. M., Vick, L. V., Dunai, C., Cruz, S. M., Razmara, A. M., Monjazeb, A. M., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.893177 · Cited by 10
“Transcriptomic Analysis of Peripheral and Tumor-Infiltrating Immune Cells Highlights Distinct Changes in Gene Expression Patterns Between NK and T Cells in Soft Tissue Sarcomas There is currently a thorough and evolving understanding of the genetic and epigenetic changes in tumor-infiltrating T cells which distinguish…”
Background
TET Proteins in the Spotlight: Emerging Concepts of Epigenetic Regulation in T Cell Biology
Tsagaratou, A. (2023) · ImmunoHorizons · doi:10.4049/immunohorizons.2200067 · Cited by 9
“However, tumor-infiltrating lymphocytes at later stages of their presence in the tumor microenvironment establish a chromatin signature that is refractory to reprogramming, and thus, they cannot regain effector function after checkpoint blockade, rendering these cells terminally dysfunctional (101).”
BackgroundInfluential
Age-associated systemic factors change central and peripheral immunity in adult male mice
van Olst, L., Kamermans, A., van der Pol, S. M. A., Rodríguez, E., Hulshof, L. A., van Dijk, R. E., Vonk, D., Schouten, M., Witte, M. E., de Vries, H. E., et al. (2023) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2023.05.004 · Cited by 10
Inverted CD8 T-Cell Exhaustion and Co-Stimulation Marker Balance Differentiate Aviremic HIV-2-Infected From Seronegative Individuals
Scharf, L., Pedersen, C. B., Johansson, E., Lindman, J. L., Olsen, L. R., Buggert, M., Wilhelmson, S., Månsson, F., Esbjörnsson, J., Biague, A. J., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.744530 · Cited by 10
Reveal the Heterogeneity in the Tumor Microenvironment of Pancreatic Cancer and Analyze the Differences in Prognosis and Immunotherapy Responses of Distinct Immune Subtypes
Wang, X., Li, L., Yang, Y., Fan, L., Ma, Y., & Mao, F. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.832715 · Cited by 10
“2017 (43) Nivolumab responsive Riaz et al.”
Lymphoid tissue residency: A key to understand Tcf-1+PD-1+ T cells
Ma, C., & Zhang, N. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1074698 · Cited by 10

Authors: Philip, M., Fairchild, L., Sun, L., Horste, E. L., Camara, S., Shakiba, M., Scott, A. C., Viale, A., Lauer, P., Merghoub, T., Hellmann, M. D., Wolchok, J. D., Leslie, C. S., & Schietinger, A.
Affiliations: Memorial Sloan Kettering Cancer Center (US)
Aduro BioTech (United States) (US)
Corresponding author: Schietinger, Andrea
ORCID: Philip, Mary
Fairchild, Lauren
Sun, Liping
Shakiba, Mojdeh
Scott, Andrew C.
Viale, Agnes
Lauer, Peter
Merghoub, Taha
Hellmann, Matthew D.
Wolchok, Jedd D.
Leslie, Christina S.
Schietinger, Andrea
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2017-05
Volume: 545
Issue: 7655
Pages: 452-456
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature22367
PMC: PMC5693219
OpenAlex: W2616155686
Cited by: 933
References: 51
Citations by year: 2026: 92 · 2025: 104 · 2024: 104 · 2023: 111 · 2022: 113 · 2021: 126 · 2020: 123 · 2019: 90 · 2018: 58 · 2017: 12
FWCI: 34.11
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Funders: National Human Genome Research Institute (U01HG007893)
National Cancer Institute (R00CA172371, K08CA158069, U54CA209975, P30CA008748)
Topics: Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords: T cell dysfunction, chromatin state, epigenetic regulation, T cell exhaustion, PD-1, immune checkpoint blockade, T cell reprogramming, transcription factors, cell surface markers, solid tumors, cancer immunotherapy
MeSH terms: Animals, Chromatin, Female, Humans, Immunologic Memory, Male, Neoplasms, Transcription Factors, Gene Expression Regulation, Neoplastic, Lymphocytes, Tumor-Infiltrating, CD8-Positive T-Lymphocytes, Gene Expression Profiling, Epigenesis, Genetic, Mice

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Chromatin states define tumour-specific T cell dysfunction and reprogramming

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