Mitochondria in T‑cell tumor immunity and tumor therapies targeting mitochondria (Review).

Mitochondria are central to cellular metabolic reprogramming, and their energy metabolism pathways are indispensable for T‑cell activation, proliferation and differentiation. Mitochondrial metabolic reprogramming enhances T‑cell activity and antitumor function. Mitochondrial dynamics, including fusion, fission and transfer, regulate T‑cell tumor immune function by modulating the number, morphology and distribution of mitochondria, which is vital for the antitumor effects of T cells. The release of mitochondrial DNA can activate multiple innate immune signaling pathways, such as cyclic GMP‑AMP synthase‑stimulator of interferon genes, Toll‑like receptor 9, and NOD‑, LRR‑, and pyrin domain‑containing protein 3, serving a complex regulatory role in shaping the tumor immunosuppressive microenvironment and T‑cell antitumor immune responses. Notably, mitochondrial dysfunction is a major driver of tumor initiation and progression. T‑cell mitochondrial metabolic reprogramming, dynamic changes and mitochondrial DNA release all affect the antitumor immunity of tumor‑infiltrating T cells. The present review focuses on the relationship between mitochondria and T‑cell antitumor immune responses, exploring the core role of mitochondria in T‑cell tumor immunity from multiple aspects, including mitochondrial energy metabolism, mitochondrial dynamics and mitochondrial DNA. In addition, the present review examines state‑of‑the‑art research on antitumor therapies targeting mitochondria from multiple perspectives, with the aim of providing a reference for developing mitochondria‑targeted antitumor immunotherapy strategies.