The DOI matches its Crossref record; 155 of the 156 references it cites were found in a registry or an index.
Molecular and cellular insights into T cell exhaustion
Open accessAbstract
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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“Other situations of chronic antigen stimulation, such as cancer or chronic viral infections, result in T cell exhaustion, characterized by the progressive loss of cytokine expression, proliferative potential, and upregulation of inhibitory receptors (immune checkpoints).”
From Autoantigen-specific CD4+ T cells acquire an exhausted phenotype and persist in human antigen-specific autoimmune diseases (2024) · cites this paper as [32]
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“Exhaustion can be partially reversed by immune checkpoint inhibitors, providing the basis for successful therapies against cancer. 32,33”
From Autoantigen-specific CD4+ T cells acquire an exhausted phenotype and persist in human antigen-specific autoimmune diseases (2024) · cites this paper as [32]
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“In TME, prolonged antigen exposure leads to T cell exhaustion, marked by losing effector functions.”
From Contrasting cytotoxic and regulatory T cell responses underlying distinct clinical outcomes to anti-PD-1 plus lenvatinib therapy in cancer (2025) · cites this paper as [24]
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“cells with an exhaustion signature (denoted exhausted, fig. S3B) overexpressing the Lag3, Tbc1d4, Sostdc1, and Tnfsf8 genes (22, 31)”
From Aging promotes reorganization of the CD4 T cell landscape toward extreme regulatory and effector phenotypes (2019) · cites this paper as [31]
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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
Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review
Wanchoo, R., Karam, S., Uppal, N. N., Barta, V. S., Deray, G., Devoe, C., Launay‐Vacher, V., Jhaveri, K. D., & on behalf of Cancer and Kidney International Network Workgroup on Immune Checkpoint Inhibitors (2017) · American Journal of Nephrology · doi:10.1159/000455014 · Cited by 15,320
The blockade of immune checkpoints in cancer immunotherapy
Pardoll, D. M. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3239 · Cited by 13,838
Nivolumab plus Ipilimumab in Advanced Melanoma
Wolchok, J. D., Kluger, H., Callahan, M. K., Postow, M. A., Rizvi, N. A., Lesokhin, A. M., Segal, N. H., Ariyan, C. E., Gordon, R.-A., Reed, K., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1302369 · Cited by 4,230
Wherry, E. J. (2011) · Nature Immunology · doi:10.1038/ni.2035 · Cited by 4,062
Self-citationRestoring function in exhausted CD8 T cells during chronic viral infection
Barber, D. L., Wherry, E. J., Masopust, D., Zhu, B., Allison, J. P., Sharpe, A. H., Freeman, G. J., & Ahmed, R. (2005) · Nature · doi:10.1038/nature04444 · Cited by 4,057
Self-citationRegulation of type I interferon responses
Ivashkiv, L. B., & Donlin, L. T. (2013) · Nature reviews. Immunology · doi:10.1038/nri3581 · Cited by 3,442
PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression
Day, C. L., Kaufmann, D. E., Kiepiela, P., Brown, J. A., Moodley, E. S., Reddy, S., Mackey, E. W., Miller, J. D., Leslie, A. J., DePierres, C., et al. (2006) · Nature · doi:10.1038/nature05115 · Cited by 2,680
Self-citationControl of Viremia in Simian Immunodeficiency Virus Infection by CD8 + Lymphocytes
Schmitz, J. E., Kuroda, M. J., Santra, S., Sasseville, V. G., Simon, M. A., Lifton, M. A., Rácz, P., Tenner‐Racz, K., Dalesandro, M. R., Scallon, B. J., et al. (1999) · Science · doi:10.1126/science.283.5403.857 · Cited by 2,167
Molecular Signature of CD8+ T Cell Exhaustion during Chronic Viral Infection
Wherry, E. J., Ha, S.-J., Kaech, S. M., Haining, W. N., Sarkar, S., Kalia, V., Subramaniam, S., Blattman, J. N., Barber, D. L., & Ahmed, R. (2007) · Immunity · doi:10.1016/j.immuni.2007.09.006 · Cited by 2,103
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Gumbleton, M., Sudan, R., Fernandes, S., Engelman, R. W., Russo, C. M., Chisholm, J. D., & Kerr, W. G. (2017) · Science Signaling · doi:10.1126/scisignal.aam5353 · Cited by 43
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Tang, X., Deng, B., Zang, A., He, X., Zhou, Y., Wang, D., Li, D., Dai, X., Chen, J., Zhang, X., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.940577 · Cited by 39
T-cell exhaustion: understanding the interface of chronic viral and autoinflammatory diseases
McKinney, E. F., & Smith, K. G. (2016) · Immunology & Cell Biology · doi:10.1038/icb.2016.81 · Cited by 36
Pirozyan, M. R., McGuire, H. M., Emran, A. A., Tseng, H.-Y., Tiffen, J. C., Lee, J. H., Carlino, M. S., Menzies, A. M., Long, G. V., Scolyer, R. A., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00372 · Cited by 34
Epigenetic mechanisms of tumor resistance to immunotherapy
Arenas-Ramirez, N., Sahin, D., & Boyman, O. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2908-7 · Cited by 36
MacDonald, K. N., Ivison, S., Hippen, K. L., Hoeppli, R. E., Hall, M., Zheng, G., Dijke, I. E., Aklabi, M. A., Freed, D. H., Rebeyka, I., et al. (2019) · Cytotherapy · doi:10.1016/j.jcyt.2019.10.011 · Cited by 30
Glucocorticoids and natural killer cells: A suppressive relationship
Muscari, I., Fierabracci, A., Adorisio, S., Moretti, M., Cannarile, L., Thi Minh Hong, V., Ayroldi, E., & Delfino, D. V. (2022) · Biochemical Pharmacology · doi:10.1016/j.bcp.2022.114930 · Cited by 32
T cell exhaustion drives osteosarcoma pathogenesis
Sun, C.-Y., Zhang, Z., Tao, L., Xu, F.-F., Li, H.-Y., Zhang, H.-Y., & Liu, W. (2021) · Annals of Translational Medicine · doi:10.21037/atm-21-3928 · Cited by 29
Lin, A., Zhang, H., Meng, H., Deng, Z., Gu, T., Luo, P., & Zhang, J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.667875 · Cited by 27
PDAC as an immune evasive disease: can 3D model systems aid to tackle this clinical problem?
Narayanan, S., Vicent, S., & Ponz-Sarvisé, M. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.787249 · Cited by 24
Tsuji, R., Komano, Y., Ohshio, K., Ishii, N., & Kanauchi, O. (2018) · Experimental Gerontology · doi:10.1016/j.exger.2018.06.028 · Cited by 20
Molecular subtype-specific responses of colon cancer cells to the SMAC mimetic Birinapant
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Ames, R. Y., Ting, L.-M., Gendlina, I., Kim, K., & Macian, F. (2017) · Infection and Immunity · doi:10.1128/iai.00364-17 · Cited by 16
Mikkilineni, L., Natrakul, D. A., Lam, N., Manasanch, E. E., Mann, J., Weissler, K. A., Wong, N., Brudno, J. N., Goff, S. L., Yang, J. C., et al. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2023.12.018 · Cited by 16
The potential role of CMC1 as an immunometabolic checkpoint in T cell immunity
Chen, Y., Gao, J., Ma, M., Wang, K., Liu, F., Yang, F., Zou, X., Cheng, Z., & Wu, D. (2024) · OncoImmunology · doi:10.1080/2162402x.2024.2344905 · Cited by 13
Kulikowska de Nałęcz, A., Ciszak, L., Usnarska-Zubkiewicz, L., Pawlak, E., Frydecka, I., Szmyrka, M., & Kosmaczewska, A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065730 · Cited by 13
New insight into the agonism of protease-activated receptors as an immunotherapeutic strategy
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Metadata
- Authors
- Wherry, E. J., & Kurachi, M.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Wherry, E. John
- Kurachi, Makoto
- Venue
- Nature Reviews Immunology
- Published
- 2015-07-24
- Volume
- 15
- Issue
- 8
- Pages
- 486-499
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- 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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