Cited by 4,652T-cell and B-cell ImmunologyCancer Immunotherapy and BiomarkersImmune Cell Function and Interaction

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Molecular and cellular insights into T cell exhaustion

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Wherry, E. John, Kurachi, Makoto·2015·Nature Reviews Immunology

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Abstract

In chronic infections and cancer, T cells are exposed to persistent antigen and/or inflammatory signals. This scenario is often associated with the deterioration of T cell function: a state called 'exhaustion'. Exhausted T cells lose robust effector functions, express multiple inhibitory receptors and are defined by an altered transcriptional programme. T cell exhaustion is often associated with inefficient control of persisting infections and tumours, but revitalization of exhausted T cells can reinvigorate immunity. Here, we review recent advances that provide a clearer molecular understanding of T cell exhaustion and reveal new therapeutic targets for persisting infections and cancer.

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Bantug, G. R., Galluzzi, L., Kroemer, G., & Hess, C. (2017) · Nature reviews. Immunology · doi:10.1038/nri.2017.99 · Cited by 436
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Gubin, M. M., Esaulova, E., Ward, J. P., Malkova, O. N., Runci, D., Wong, P., Noguchi, T., Arthur, C. D., Meng, W., Alspach, E., et al. (2018) · Cell · doi:10.1016/j.cell.2018.09.030 · Cited by 422
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Tang, N., Cheng, C. Y., Zhang, X., Qiao, M., Li, N., Mu, W., Wei, X., Han, W., & Wang, H. (2020) · JCI Insight · doi:10.1172/jci.insight.133977 · Cited by 424
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Lei, A., Yu, H., Lu, S., Lu, H., Ding, X., Tan, T., Zhang, H., Zhu, M., Tian, L., Wang, X., et al. (2023) · Nature Immunology · doi:10.1038/s41590-023-01687-8 · Cited by 326
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Zhang, S., Zhang, E., Long, J., Hu, Z., Peng, J. W., Liu, L., Tang, F., Li, L., Ouyang, Y., & Zeng, Z. (2019) · Cancer Science · doi:10.1111/cas.13996 · Cited by 303
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Byrne, A., Savas, P. S., Sant, S. A., Li, R., Virassamy, B., Luen, S. J., Beavis, P. A., Mackay, L. K., Neeson, P. J., & Loi, S. (2020) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-0333-y · Cited by 309
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Li, S., Siriwon, N., Zhang, X., Yang, S., Jin, T., He, F., Kim, K. G., Mac, J., Lu, Z., Wang, S. P., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-0867 · Cited by 309
Adaptive Immune Resistance Emerges from Tumor-Initiating Stem Cells
Miao, Y., Yang, H., Levorse, J., Yuan, S., Polak, L., Sribour, M., Singh, B., Rosenblum, M. D., & Fuchs, E. (2019) · Cell · doi:10.1016/j.cell.2019.03.025 · Cited by 299
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Wachsmuth, L. P., Patterson, M. T., Eckhaus, M., Venzon, D. J., Gress, R. E., & Kanakry, C. G. (2019) · Journal of Clinical Investigation · doi:10.1172/jci124218 · Cited by 299
AP-1 Transcription Factors as Regulators of Immune Responses in Cancer
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Immunometabolism in early and late stages of rheumatoid arthritis
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Metabolic and Epigenetic Coordination of T Cell and Macrophage Immunity
Phan, A. T., Goldrath, A. W., & Glass, C. K. (2017) · Immunity · doi:10.1016/j.immuni.2017.04.016 · Cited by 296
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Challenges and potential of PD-1/PD-L1 checkpoint blockade immunotherapy for glioblastoma
Wang, X., Guo, G., Guan, H., Yu, Y., Lu, J., & Yu, J. (2019) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-019-1085-3 · Cited by 292
TOX promotes the exhaustion of antitumor CD8+ T cells by preventing PD1 degradation in hepatocellular carcinoma
Wang, X., He, Q., Shen, H., Xia, A., Tian, W., Yu, W., & Sun, B. (2019) · Journal of Hepatology · doi:10.1016/j.jhep.2019.05.015 · Cited by 287
Conventional type I dendritic cells maintain a reservoir of proliferative tumor-antigen specific TCF-1+ CD8+ T cells in tumor-draining lymph nodes
Schenkel, J. M., Herbst, R. H., Canner, D. A., Li, A., Hillman, M., Shanahan, S.-L., Gibbons, G., Smith, O. C. G., Kim, J. Y., Westcott, P. M. K., et al. (2021) · Immunity · doi:10.1016/j.immuni.2021.08.026 · Cited by 297
An early history of T cell-mediated cytotoxicity
Golstein, P., & Griffiths, G. M. (2018) · Nature reviews. Immunology · doi:10.1038/s41577-018-0009-3 · Cited by 303
LAG-3 and PD-1 synergize on CD8+ T cells to drive T cell exhaustion and hinder autocrine IFN-γ-dependent anti-tumor immunity
Andrews, L. P., Butler, S. C., Cui, J., Cillo, A. R., Cardello, C., Liu, C., Brunazzi, E. A., Baessler, A., Xie, B., Kunning, S. R., et al. (2024) · Cell · doi:10.1016/j.cell.2024.07.016 · Cited by 302
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T-cell exhaustion induced by continuous bispecific molecule exposure is ameliorated by treatment-free intervals
Philipp, N., Pasikhani, M. K., Nicholls, A., Vick, B., Wulf, J., Straub, T., Scheurer, M., Muth, A., Hänel, G., Nixdorf, D., et al. (2022) · Blood · doi:10.1182/blood.2022015956 · Cited by 289
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Smith, L. K., Boukhaled, G. M., Condotta, S. A., Mazouz, S., Guthmiller, J. J., Vijay, R., Butler, N. S., Bruneau, J., Shoukry, N. H., Krawczyk, C. M., et al. (2018) · Immunity · doi:10.1016/j.immuni.2018.01.006 · Cited by 287
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Kim, C. G., Kim, K. H., Pyo, K., Xin, C.-F., Hong, M. H., Ahn, B., Kim, Y., Choi, S. J., Yoon, H. I., Lee, J. G., et al. (2019) · Annals of Oncology · doi:10.1093/annonc/mdz123 · Cited by 286
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Tong, C., Zhang, Y., Liu, Y., Ji, X., Zhang, W., Guo, Y., Han, X., Ti, D., Dai, H., Wang, C., et al. (2020) · Blood · doi:10.1182/blood.2020005278 · Cited by 279
Advances in cancer immunotherapy: historical perspectives, current developments, and future directions
Zhang, M., Liu, C.-J., Tu, J., Tang, M., Ashrafizadeh, M., Nabavi, N., Sethi, G., Zhao, P., & Liu, S. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02305-x · Cited by 324
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Freed-Pastor, W. A., Lambert, L. J., Ely, Z. A., Pattada, N. B., Bhutkar, A., Eng, G., Mercer, K. L., Garcia, A. P., Lin, L., Rideout, W. M., et al. (2021) · Cancer Cell · doi:10.1016/j.ccell.2021.07.007 · Cited by 273
T cell senescence and CAR-T cell exhaustion in hematological malignancies
Kasakovski, D., Xu, L., & Li, Y. (2018) · Journal of Hematology & Oncology · doi:10.1186/s13045-018-0629-x · Cited by 282
Human γδ T cells are quickly reconstituted after stem-cell transplantation and show adaptive clonal expansion in response to viral infection
Ravens, S., Schultze-Florey, C. R., Raha, S., Sandrock, I., Drenker, M., Oberdörfer, L., Reinhardt, A., Ravens, I., Beck, M., Geffers, R., et al. (2017) · Nature Immunology · doi:10.1038/ni.3686 · Cited by 271
Hypoxia drives CD39-dependent suppressor function in exhausted T cells to limit antitumor immunity
Vignali, P. D. A., DePeaux, K., Watson, M. J., Ye, C., Ford, B. R., Lontos, K., McGaa, N. K., Scharping, N. E., Menk, A. V., Robson, S. C., et al. (2023) · Nature Immunology · doi:10.1038/s41590-022-01379-9 · Cited by 269
Age-Related Decline in Primary CD8+ T Cell Responses Is Associated with the Development of Senescence in Virtual Memory CD8+ T Cells
Quinn, K. M., Fox, A., Harland, K. L., Russ, B. E., Li, J., Nguyen, T. H. O., Loh, L., Olshanksy, M., Naeem, H., Tsyganov, K., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.05.057 · Cited by 262
Reversing insufficient photothermal therapy-induced tumor relapse and metastasis by regulating cancer-associated fibroblasts
Li, X., Yong, T., Wei, Z., Bie, N., Zhang, X., Zhan, G., Li, J., Qin, J., Yu, J., Zhang, B., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-30306-7 · Cited by 272
A Convergence-Based Framework for Cancer Drug Resistance
Konieczkowski, D. J., Johannessen, C. M., & Garraway, L. A. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.03.025 · Cited by 258
Effector, Memory, and Dysfunctional CD8+T Cell Fates in the Antitumor Immune Response
Reiser, J., & Banerjee, A. (2016) · Journal of Immunology Research · doi:10.1155/2016/8941260 · Cited by 262
The dawn of vaccines for cancer prevention
Finn, O. J. (2017) · Nature reviews. Immunology · doi:10.1038/nri.2017.140 · Cited by 257
Association Between Expression Level of PD1 by Tumor-Infiltrating CD8+ T Cells and Features of Hepatocellular Carcinoma
Kim, H., Song, G., Park, S., Kim, M. H., Kim, M. H., Kang, H. J., Yoo, C., Kim, K. H., Kim, K. H., Eo, S.-K., et al. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.08.030 · Cited by 258
Multiplexed imaging mass cytometry of the chemokine milieus in melanoma characterizes features of the response to immunotherapy
Hoch, T., Schulz, D., Eling, N., Gómez, J. M. M., Levesque, M. P., & Bodenmiller, B. (2022) · Science Immunology · doi:10.1126/sciimmunol.abk1692 · Cited by 253

Authors: Wherry, E. J., & Kurachi, M.
Affiliations: University of Pennsylvania (US)
Corresponding author: Wherry, E. John
Kurachi, Makoto
ORCID: Wherry, E. John
Kurachi, Makoto
Venue: Nature Reviews Immunology
Publisher: Springer Science and Business Media LLC
Published: 2015-07-24
Volume: 15
Issue: 8
Pages: 486-499
ISSN: 1474-1733 (ISSN-L)
1474-1741
DOI: 10.1038/nri3862
PMC: PMC4889009
OpenAlex: W1910012553
Cited by: 4,652
References: 156
Citations by year: 2026: 563 · 2025: 494 · 2024: 518 · 2023: 508 · 2022: 517 · 2021: 551 · 2020: 441 · 2019: 381 · 2018: 306 · 2017: 227 · 2016: 129 · 2015: 12
FWCI: 21.14
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature reviews. Immunology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: U.S. Public Health Service (HHSN266200500030C)
National Institute of Allergy and Infectious Diseases (HHSN266200500030C, AI 082630, R01AI105343, AI095608, AI105343, AI112521, P01AI112521, U01AI095608, U19AI082630)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
Keywords: T cell exhaustion, chronic viral infection, cancer immunotherapy, inhibitory receptors, persistent antigen, inflammatory signals, transcriptional programs, therapeutic target
MeSH terms: Bacterial Infections, Gene Expression Regulation, Humans, Immunologic Memory, Lymphocyte Activation, Neoplasms, T-Lymphocytes, Cytotoxic, Transcription, Genetic, Virus Diseases, Signal Transduction, Cytokines, Clonal Anergy, CD57 Antigens, T-Lymphocytes, Regulatory

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Molecular and cellular insights into T cell exhaustion

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