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Updated: Jun 7, 2025

Real-time Monitoring of Mitochondrial Respiration in Cytokine-differentiated Human Primary T Cells
Published on: October 19, 2021
Targeting mitochondria: restoring the antitumor efficacy of exhausted T cells
Mei-Qi Yang1,2, Shu-Ling Zhang1,2, Li Sun1,2
1Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
Abstract:
Immune checkpoint blockade therapy has revolutionized cancer treatment, but resistance remains prevalent, often due to dysfunctional tumor-infiltrating lymphocytes. A key contributor to this dysfunction is mitochondrial dysfunction, characterized by defective oxidative phosphorylation, impaired adaptation, and depolarization, which promotes T cell exhaustion and severely compromises antitumor efficacy. This review summarizes recent advances in restoring the function of exhausted T cells through mitochondria-targeted strategies, such as metabolic remodeling, enhanced biogenesis, and regulation of antioxidant and reactive oxygen species, with the aim of reversing the state of T cell exhaustion and improving the response to immunotherapy. A deeper understanding of the role of mitochondria in T cell exhaustion lays the foundation for the development of novel mitochondria-targeted therapies and opens a new chapter in cancer immunotherapy.
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