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Exhaustion and senescence: two crucial dysfunctional states of T cells in the tumor microenvironment
Open accessAbstract
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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“T cell senescence is irreversible, as opposed to their anergy and exhaustion, both of which are considered reversible [31, 38–40].”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [39]
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Metadata
- Authors
- Zhao, Y., Shao, Q., & Peng, G.
- Affiliations
- Jiangsu University (CN)
- Saint Louis University (US)
- Corresponding author
- Peng, Guangyong
- Venue
- Cellular & Molecular Immunology
- Published
- 2019-12-18
- Volume
- 17
- Issue
- 1
- Pages
- 27-35
- ISSN
- 1672-7681 (ISSN-L)
- 2042-0226
- 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
- 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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