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REVIEW article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1476904
This article is part of the Research Topic Dissecting the Role of T Cell Exhaustion in Cancer Progression: A Multifaceted Approach View all articles

CD8 + T cell Exhaustion and Its Regulatory Mechanisms in the Tumor Microenvironment: Key to the Success of Immunotherapy

Provisionally accepted
Biao Zhang Biao Zhang 1Jinming Liu Jinming Liu 1Yuying Mo Yuying Mo 1Kexin Zhang Kexin Zhang 2Bingqian Huang Bingqian Huang 3*Dong Shang Dong Shang 1*
  • 1 First Affiliated Hospital, Dalian Medical University, Dalian, China
  • 2 Dalian Medical University, Dalian, Liaoning, China
  • 3 Westlake University, Hangzhou, Zhejiang, China

The final, formatted version of the article will be published soon.

    A steady dysfunctional state caused by chronic antigen stimulation in the tumor microenvironment (TME) is known as CD8 + T cell exhaustion. Exhausted-like CD8 + T cells (CD8 + Tex) displayed decreased effector and proliferative capabilities, elevated co-inhibitory receptor generation, decreased cytotoxicity, and changes in metabolism and transcription. TME induces T cell exhaustion through long-term antigen stimulation, upregulation of immune checkpoints, recruitment of immunosuppressive cells, and secretion of immunosuppressive cytokines. CD8 + Tex may be both the reflection of cancer progression and the reason for poor cancer control. The successful outcome of the current cancer immunotherapies, which include immune checkpoint blockade and adoptive cell treatment, depends on CD8 + Tex. In this review, we are interested in the intercellular signaling network of immune cells interacting with CD8 + Tex. These findings provide a unique and detailed perspective, which is helpful in changing this completely unpopular state of hypofunction and intensifying the effect of immunotherapy.

    Keywords: CD8 + T cell, t cell exhaustion, Tumor Microenvironment, Immune checkpoint blockade, adoptive T cell treatment

    Received: 06 Aug 2024; Accepted: 04 Sep 2024.

    Copyright: © 2024 Zhang, Liu, Mo, Zhang, Huang and Shang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Bingqian Huang, Westlake University, Hangzhou, 310024, Zhejiang, China
    Dong Shang, First Affiliated Hospital, Dalian Medical University, Dalian, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.