The DOI matches its Crossref record; 119 of the 120 references it cites were found in a registry or an index.
T Cell Dysfunction and Exhaustion in Cancer
Open accessAbstract
Tumor immunotherapy is a promising therapeutic strategy for patients with advanced cancers. T cells are key mediators of antitumor function that specifically recognize and react to tumor-expressing antigens and have proven critical for cancer immunotherapy. However, T cells are not as effective against cancer as expected. This is partly because T cells enter a dysfunctional or exhausted state, which is characterized by sustained expression of inhibitory receptors and a transcriptional state distinct from that of functional effector or memory T cells. T cell dysfunction induces the out of control of tumors. Recently, T cell dysfunction has been investigated in many experimental and clinical settings. The molecular definition of T cell dysfunction and the underlying causes of the T cell dysfunction has been advanced regardless of the fact that the pathways involved are not well elucidated, which proposing promising therapeutic opportunities in clinic. In this review, we will discuss the recent advances in the molecular mechanisms that affect TME and induce T cell dysfunction, and the development of promising immunotherapies to counteract the mechanisms of tumor-induced T cell dysfunction. Better understanding these underlying mechanisms may lead to new strategies to improve the clinical outcome of patients with cancer.
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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 [40]
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Cites
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“Similarly, TCF-1 is also required for the stemlike functions of TCF1+PD-1+ TILs, which were detected in the blood of patients with melanoma and who had responded to checkpoint blockade (Siddiqui et al., 2019).”
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Self-citationMolecular and cellular insights into T cell exhaustion
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“In addition, NO alone can suppress CD8+ T cells by inhibiting the phosphorylation and activation of JAK3 and STAT5 transcription factors, as well as inducing T-cell apoptosis (Wu et al., 2015).”
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“However, when antigen-experienced T cells are chronically exposed to the same antigen, substantial alterations in T cell activation and differentiation may occur, leading to T cell “dysfunction” or “exhaustion” (Wherry, 2011; Schietinger and Greenberg, 2014).”
BackgroundMetabolic Competition in the Tumor Microenvironment Is a Driver of Cancer Progression
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“Interestingly, inhibition of EZH2 in ovarian and colorectal cancer patients resulted in increased of CXCL9 and CXCL10 production and augmented the infiltration of T cells that eliminate tumors (Nagarsheth et al., 2016; Jones et al., 2018).”
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1 of the 120 references couldn’t be matched to a known paper.
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The foundations of immune checkpoint blockade and the ipilimumab approval decennial
Korman, A. J., Garrett-Thomson, S. C., & Lönberg, N. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00345-8 · Cited by 572
Immunosenescence: a key player in cancer development
Lian, J., Yue, Y., Yu, W., & Zhang, Y. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00986-z · Cited by 510
Self-citationResistance Mechanisms of Anti-PD1/PDL1 Therapy in Solid Tumors
Lei, Q., Wang, D., Sun, K., Wang, L., & Zhang, Y. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00672 · Cited by 431
Self-citationImmune evasion in cancer: mechanisms and cutting-edge therapeutic approaches
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Bao, H., Cao, J., Chen, M., Min, C., Chen, W., Chen, X., Chen, Y., Chen, Y., Chen, Y., Chen, Z., et al. (2023) · Science China Life Sciences · doi:10.1007/s11427-023-2305-0 · Cited by 402
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Metadata
- Authors
- Zhang, Z., Liu, S., Zhang, B., Qiao, L., Zhang, Y., & Zhang, Y.
- Affiliations
- First Affiliated Hospital of Zhengzhou University (CN)
- Northwestern University (US)
- Loyola University Chicago (US)
- Venue
- Frontiers in Cell and Developmental Biology
- Publisher
- Frontiers Media SA
- Published
- 2020-02-11
- Volume
- 8
- Pages
- 17-17
- ISSN
- 2296-634X (ISSN-L)
- PMC
- PMC7027373
- OpenAlex
- W3006138994
- Cited by
- 385
- References
- 120
- Citations by year
- 2026: 39 · 2025: 52 · 2024: 70 · 2023: 64 · 2022: 65 · 2021: 60 · 2020: 34
- FWCI
- 5.99
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Cell and Developmental Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (U1804281, 81771781, 81702810, 81773060)
- 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, T cell exhaustion, cancer immunotherapy, tumor microenvironment, inhibitory receptors, antitumor immunity, immunotherapy resistance
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