REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1646138
Mitochondria-targeted strategies in tumor immunity
Provisionally accepted
- 1Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, China
- 2Houston Methodist, Houston, United States
- 3Medical College of Wisconsin, Milwaukee, United States
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Mitochondria, as regulators of cellular energy production and metabolism, play a crucial role in tumor growth and survival. Tumors are reprogrammed to accommodate rapid proliferation through the Warburg effect. This reprogramming leads to the accumulation of metabolites such as lactate and ketone bodies, thereby lowering the pH of the tumor microenvironment, inhibiting the activity of effector T cells and NK cells, while promoting the infiltration of regulatory T cells and MDSCs, forming an immunosuppressive microenvironment. ROS produced by mitochondria can affect immune cell function by modulating their signaling pathways. Mitochondria also release DAMPs, which activate the antigen-presenting capacity of dendritic cells and initiate anti-tumor immune responses. Currently, various methods have been employed, such as DLCs modifications and mitochondrial targeted delivery, which enable drugs to penetrate the lipid bilayer and enter the mitochondria, thereby helping to reduce immunosuppression in the tumor microenvironment. In this review, we will discuss the impact of mitochondria on tumor immunity, strategies to target tumor cell mitochondria, and progress on the discovery of mitochondria-targeted drugs to enhance tumor immunity, providing potential directions for developing new cancer therapeutic strategies.
Keywords: Mitochondria targeted, Triphenylphosphonium, TME, Cancer, Immunotherapy
Received: 12 Jun 2025; Accepted: 14 Oct 2025.
Copyright: © 2025 Cheng, Wang, Johnson and You. 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: Ming You, myou@houstonmethodist.org
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