REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicFormation and Remodeling of Immunological Niches in Tumors: Organ-Specific Mechanisms and Inflammatory Parallels: Volume IIView all 16 articles
Dissecting the Role of T Cell Exhaustion in Cancer Progression: A Multifaceted Approach
Provisionally accepted
- 1The People's Hospital of Gaozhou, Maoming, China
- 2Shengjing Hospital of China Medical University, Shenyang, China
- 3The First Affiliated Hospital of China Medical University, Shenyang, China
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This article thoroughly explores the crucial role of T cell exhaustion in the process of tumor immune escape, comprehensively explaining its key characteristics, such as dynamic plasticity, heterogeneity, and epigenetic reprogramming. The article first elaborates on the complex interaction between immune surveillance and tumor escape, and then clarifies the core position of T cells in anti-tumor immunity and the evolution of the "exhaustion" concept, covering various research fields from chronic infections to the tumor microenvironment (TME). It provides a detailed analysis of the origin, differentiation pathways, and dynamic plasticity of exhausted T cells, revealing the possibility of functional recovery under specific conditions. At the same time, the article analyzes the profound influence of various factors in the TME (such as metabolic stress, immune suppression networks, and stromal interaction interfaces) on the process of T cell exhaustion. It conducts in-depth research on the molecular characteristics of exhausted T cells (including surface marker characteristics, transcriptional regulatory networks, and metabolic reprogramming characteristics), providing potential therapeutic targets for precision medicine. In the clinical translation aspect, this study clarifies the cutting-edge exploration achievements of diagnostic biomarkers, such as the exhausted subtypes defined by single-cell multi-omics technology, the prognostic value of TCR clonal dynamics, and the innovation of treatment strategies, including the "re-mobilization window" theory in PD-1 blockade, the synergistic effect of epigenetic drugs, the temporal and spatial selection in metabolic intervention, and the application of engineered cell therapies. This study systematically integrates the latest progress in the field of T cell exhaustion, providing comprehensive and profound theoretical support and innovative ideas for addressing challenges in tumor immunotherapy.
Keywords: t cell exhaustion, TME, immune escape, epigenetic reprogramming, clinical translation, Immunotherapy
Received: 13 Jun 2025; Accepted: 05 Nov 2025.
Copyright: © 2025 Huang, Li and Song. 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: Shiwen Song, 1326969425@qq.com
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