Cited by 388Cancer Immunotherapy and BiomarkersT-cell and B-cell ImmunologyImmunotherapy and Immune Responses

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Exhaustion and senescence: two crucial dysfunctional states of T cells in the tumor microenvironment

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Zhao, Yangjing, Shao, Qixiang, Peng, Guangyong·2020·Cellular & Molecular Immunology

DOI 10.1038/s41423-019-0344-8PMC PMC6952436

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Abstract

The failure of a massive influx of tumor-infiltrating T lymphocytes to eradicate tumor cells in the tumor microenvironment is mainly due to the dysfunction of T cells hyporesponsive to tumors. T-cell exhaustion and senescence induced by malignant tumors are two important dysfunctional states that coexist in cancer patients, hindering effective antitumor immunity and immunotherapy and sustaining the suppressive tumor microenvironment. Although exhausted and senescent T cells share a similar dysfunctional role in antitumor immunity, they are distinctly different in terms of generation, development, and metabolic and molecular regulation during tumor progression. Here, we discuss the unique phenotypic and functional characteristics of these two types of dysfunctional T cells and their roles in tumor development and progression. In addition, we further discuss the potential molecular and metabolic signaling pathways responsible for the control of T-cell exhaustion and senescence in the suppressive tumor microenvironment. Understanding these critical and fundamental features should facilitate rethinking the unresponsiveness to current immunotherapies in clinical patients and lead to further development of novel and effective strategies that target different types of dysfunctional T cells to enhance cancer immunotherapy.

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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
The blockade of immune checkpoints in cancer immunotherapy
Pardoll, D. M. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3239 · Cited by 13,838
A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., & Pereira-Smith, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9363 · Cited by 7,477
The limited in vitro lifetime of human diploid cell strains
Hayflick, L. (1965) · Experimental Cell Research · doi:10.1016/0014-4827(65)90211-9 · Cited by 5,876
The senescence-associated secretory phenotype: the dark side of tumor suppression
Coppé, J.-P., Desprez, P.-Y., Krtolica, A., & Campisi, J. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-121808-102144 · Cited by 5,206
Molecular and cellular insights into T cell exhaustion
Wherry, E. J., & Kurachi, M. (2015) · Nature Reviews Immunology · doi:10.1038/nri3862 · Cited by 4,652
Cellular senescence: when bad things happen to good cells
Campisi, J., & d'Adda di Fagagna, F. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2233 · Cited by 4,441
Immune Checkpoint Blockade: A Common Denominator Approach to Cancer Therapy
Topalian, S. L., Drake, C. G., & Pardoll, D. M. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.03.001 · Cited by 4,229
T cell exhaustion
Wherry, E. J. (2011) · Nature Immunology · doi:10.1038/ni.2035 · Cited by 4,062
Metabolic Competition in the Tumor Microenvironment Is a Driver of Cancer Progression
Chang, C.-H., Qiu, J., O’Sullivan, D., Buck, M. D., Noguchi, T., Curtis, J. D., Chen, Q., Gindin, M., Gubin, M. M., van der Windt, G. J. W., et al. (2015) · Cell · doi:10.1016/j.cell.2015.08.016 · Cited by 3,331

Show all 140 references

Research works printed but not linked: 2

Fourcade, J. et al. Upregulation of Tim-3 and PD-1 expression is associated with tumor antigen-specific CD8(+) T cell dysfunction in melanoma patients. J. Exp. Med. 207, 2175–2186 (2010). · DOI · Paper page
Brenchley, J. M. et al. Expression of CD57 defines replicative senescence and antigen-induced apoptotic death of CD8+ T cells. Blood 101, 2711–2720 (2003). · DOI · Paper page

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Additional file 1 of High proportion of circulating CD8 + CD28- senescent T cells is an independent predictor of distant metastasis in nasopharyngeal carcinoma after radiotherapy
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Additional file 4 of Portraying the dark side of endogenous IFN-λ for promoting cancer progression and immunoevasion in pan-cancer
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Additional file 9 of The inter-link of ageing, cancer and immunity: findings from real-world retrospective study
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Additional file 3 of Portraying the dark side of endogenous IFN-λ for promoting cancer progression and immunoevasion in pan-cancer
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Additional file 3 of The inter-link of ageing, cancer and immunity: findings from real-world retrospective study
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Additional file 8 of High proportion of circulating CD8 + CD28- senescent T cells is an independent predictor of distant metastasis in nasopharyngeal carcinoma after radiotherapy
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Additional file 2 of Portraying the dark side of endogenous IFN-λ for promoting cancer progression and immunoevasion in pan-cancer
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Additional file 5 of Portraying the dark side of endogenous IFN-λ for promoting cancer progression and immunoevasion in pan-cancer
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Additional file 9 of High proportion of circulating CD8 + CD28- senescent T cells is an independent predictor of distant metastasis in nasopharyngeal carcinoma after radiotherapy
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Additional file 8 of The inter-link of ageing, cancer and immunity: findings from real-world retrospective study
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Self-citation
Impaired ex vivo T-cell expansion before leukapheresis is associated with out-of-specification tisagenlecleucel manufacturing in pediatric CD19+ALL
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Authors: Zhao, Y., Shao, Q., & Peng, G.
Affiliations: Jiangsu University (CN)
Saint Louis University (US)
Corresponding author: Peng, Guangyong
ORCID: Zhao, Yangjing
Shao, Qixiang
Peng, Guangyong
Venue: Cellular & Molecular Immunology
Publisher: Springer Science and Business Media LLC
Published: 2019-12-18
Volume: 17
Issue: 1
Pages: 27-35
ISSN: 1672-7681 (ISSN-L)
2042-0226
DOI: 10.1038/s41423-019-0344-8
PMC: PMC6952436
OpenAlex: W2995437528
Cited by: 382
References: 140
Citations by year: 2026: 39 · 2025: 90 · 2024: 70 · 2023: 59 · 2022: 61 · 2021: 45 · 2020: 18
FWCI: 2.95
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Cellular and Molecular Immunology (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: American Cancer Society (RSG-10-160-01-LIB)
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 exhaustion, T cell senescence, tumor-infiltrating T cells, tumor microenvironment, antitumor immunity, immunotherapy resistance, T cell metabolism, metabolic signaling pathways, cancer immunotherapy
MeSH terms: Animals, Humans, Immunotherapy, Neoplasms, T-Lymphocytes, Lymphocytes, Tumor-Infiltrating, Cellular Senescence, Tumor Microenvironment

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Exhaustion and senescence: two crucial dysfunctional states of T cells in the tumor microenvironment

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