Mitochondria: from powerhouses of cells to hubs in antitumor immunity

While immune checkpoint inhibitors and chimeric antigen receptor T-cell (CAR-T) therapies constitute the cornerstone of current immunotherapy, their efficacy is often limited by, most notably, the immunosuppressive tumor microenvironment. Recently, mitochondria are recognized as pivotal metabolic-immune hubs that critically support tumor progression, metastasis, and immune evasion. However, this insight has not yet translated into a clear understanding of the underlying mechanisms or their therapeutic potential. This review summarizes the role of mitochondria in cellular metabolic regulation, with a focus on mitochondrial−mediated metabolic reprogramming in cancer and immune cells within the tumor microenvironment. We then discuss therapeutic opportunities to potentiate antitumor immunity by targeting mitochondrial reprogramming in cancer and CAR-T cells. Finally, we offer a forward-looking perspective on emerging mitochondria−targeted strategies, such as mitochondrial vaccines, precise mtDNA editing, and engineered mitochondrial transplantation.