Nutritional intervention alleviates T cell exhaustion and empowers anti-tumor immunity

T cells are central mediators of adaptive immunity, playing a pivotal role in eliminating pathogens and tumor cells. In the context of chronic infections and cancer, however, persistent antigenic stimulation drives T cells into a state of exhaustion characterized by diminished effector function, sustained expression of inhibitory receptors, and profound metabolic reprogramming. Emerging evidence indicates that T cell exhaustion is not irreversible and can be alleviated through immune checkpoint blockade, such as targeting PD-1. Moreover, increasing attention has been directed toward the role of intracellular metabolic pathways in shaping T cell fate and function. Strategies aimed at enhancing nutrient availability and metabolic fitness offer an additional avenue to restore T cell activity. This review highlights recent advances in reversing T cell exhaustion through immune checkpoint inhibitors and nutritional interventions, providing novel insights into the precision and personalization of cancer immunotherapy.

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Publication Details

Journal
Frontiers in Immunology
Published
2025-12-19
DOI
https://doi.org/10.3389/fimmu.2025.1689317
Primary Topic
Cancer Immunotherapy and Biomarkers
Type
article
Field-Weighted Citation Impact
0.00

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article

Nutritional intervention alleviates T cell exhaustion and empowers anti-tumor immunity

Peng Li, Wenhui Yuan, Yuqi Xu, Ke Li
Frontiers in Immunology
Cancer Immunotherapy and Biomarkers
article

Nutritional intervention alleviates T cell exhaustion and empowers anti-tumor immunity

Peng Li, Wenhui Yuan, Yuqi Xu, Ke Li
article en

Abstract

T cells are central mediators of adaptive immunity, playing a pivotal role in eliminating pathogens and tumor cells. In the context of chronic infections and cancer, however, persistent antigenic stimulation drives T cells into a state of exhaustion characterized by diminished effector function, sustained expression of inhibitory receptors, and profound metabolic reprogramming. Emerging evidence indicates that T cell exhaustion is not irreversible and can be alleviated through immune checkpoint blockade, such as targeting PD-1. Moreover, increasing attention has been directed toward the role of intracellular metabolic pathways in shaping T cell fate and function. Strategies aimed at enhancing nutrient availability and metabolic fitness offer an additional avenue to restore T cell activity. This review highlights recent advances in reversing T cell exhaustion through immune checkpoint inhibitors and nutritional interventions, providing novel insights into the precision and personalization of cancer immunotherapy.

Frontiers in ImmunologyVol. 16
Sun Yat-sen University (CN), Jinan University (CN), The Seventh Affiliated Hospital of Sun Yat-sen University (CN), Zhuhai People's Hospital (CN), Shenzhen Institutes of Advanced Technology (CN), Shenzhen Technology University (CN)
National Natural Science Foundation of China, Basic and Applied Basic Research Foundation of Guangdong Province
Openalex Percentile: Top 43%
Cancer Immunotherapy and Biomarkers
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Nutritional intervention alleviates T cell exhaustion and empowers anti-tumor immunity — Peng Li, Wenhui Yuan, et al. · Frontiers in Immunology (2025) | TGRS Research Map | TGRS