Cited by 386Cancer Immunotherapy and BiomarkersT-cell and B-cell ImmunologyImmunotherapy and Immune Responses

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T Cell Dysfunction and Exhaustion in Cancer

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Zhang, Zhen, Liu, Shasha, Zhang, Bin, Qiao, Liang, Zhang, Yi, Zhang, Yi·2020·Frontiers in Cell and Developmental Biology

DOI 10.3389/fcell.2020.00017PMC PMC7027373

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Abstract

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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Additional file 2 of NF-κB Activator 1 downregulation in macrophages activates STAT3 to promote adenoma-adenocarcinoma transition and immunosuppression in colorectal cancer
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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)
ORCID: Zhang, Zhen
Liu, Shasha
Zhang, Bin
Qiao, Liang
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)
DOI: 10.3389/fcell.2020.00017
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: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
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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T Cell Dysfunction and Exhaustion in Cancer

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