ID | 63731 |
FullText URL | |
Author |
Nagasaki, Joji
Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Togashi, Yosuke
Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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Abstract | In T-cell biology, ‘exhaustion’ was initially described as a hyporesponsive state in CD8+ T cells during chronic infections. Recently, exhaustion has been recognized as a T-cell dysfunctional state in the tumor microenvironment (TME). The term ‘exhaustion’ is used mainly to refer to effector T cells with a reduced capacity to secrete cytokines and an increased expression of inhibitory receptors. The up-regulation of exhaustion-related inhibitory receptors, including programmed cell death protein 1 (PD-1), in such T cells has been associated with the development of tumors, prompting the development of immune checkpoint inhibitors. In addition to CD8+ T cells, CD4+ T cells, including the regulatory T (Treg) cell subset, perform a wide variety of functions within the adaptive immune system. Up-regulation of the same inhibitory receptors that are associated with CD8+ T-cell exhaustion has also been identified in CD4+ T cells in chronic infections and cancers, suggesting a similar CD4+ T-cell exhaustion phenotype. For instance, high expression of PD-1 has been observed in Treg cells in the TME, and such Treg cells can play an important role in the resistance to PD-1 blockade therapies. Furthermore, recent progress in single-cell RNA sequencing has shown that CD4+ T cells with cytotoxic activity are also vulnerable to exhaustion. In this review, we will discuss novel insights into various exhausted T-cell subsets, which could reveal novel therapeutic targets and strategies to induce a robust anti-tumor immune response.
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Keywords | CD4(+) T cell
cytotoxic CD4(+ )T cell
regulatory T cell
T-cell exhaustion
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Note | This is a pre-copyedited, author-produced version of an article accepted for publication in [International Immunology] following peer review. The version of record [Joji Nagasaki, Yosuke Togashi, A variety of ‘exhausted’ T cells in the tumor microenvironment, International Immunology, Volume 34, Issue 11, November 2022, Pages 563–570, https://doi.org/10.1093/intimm/dxac013] is available online at: [https://doi.org/10.1093/intimm/dxac013]
This fulltext is available in April 2023. |
Published Date | 2022-4-23
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Publication Title |
International Immunology
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Volume | volume34
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Issue | issue11
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Publisher | Oxford University Press
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Start Page | 563
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End Page | 570
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ISSN | 1460-2377
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Content Type |
Journal Article
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language |
English
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OAI-PMH Set |
岡山大学
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Copyright Holders | © The Author(s) 2022.
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File Version | author
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PubMed ID | |
DOI | |
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Related Url | isVersionOf https://doi.org/10.1093/intimm/dxac013
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Citation | Joji Nagasaki, Yosuke Togashi, A variety of ‘exhausted’ T cells in the tumor microenvironment, International Immunology, Volume 34, Issue 11, November 2022, Pages 563–570, https://doi.org/10.1093/intimm/dxac013
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Funder Name |
Ministry of Education, Culture, Sports, Science and Technology
Japan Agency for Medical Research and Development
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助成番号 | 20H03694
19ck0106521h0001
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