Cancer immunotherapy and mitochondrial metabolic reprogramming

The complexity of the tumor microenvironment often leads to resistance to cancer immunotherapy, and mitochondrial metabolic reprogramming is an important mechanism underlying tumor immune evasion. Treatment selection and response prediction remain challenging because the mechanisms of resistance and changes in the tumor immune microenvironment are incompletely understood. Therefore, a comprehensive understanding of immunotherapy resistance will facilitate the development of targeted strategies to overcome resistance. This review synthesizes the manifestations and consequences of mitochondrial metabolic reprogramming in tumor cells and summarizes how tumor-derived metabolites shape an immunosuppressive TME. It focuses on how mitochondrial metabolic reprogramming in antitumor immune cells, including CD8 + T cells, dendritic cells, M1-like tumor-associated macrophages, and natural killer cells, and in immunosuppressive cells, including regulatory T cells, myeloid-derived suppressor cells, and M2-like tumor-associated macrophages, contributes to the exhaustion of antitumor immunity and promotes tumor immune evasion. This review examines how mitochondrial metabolism can be targeted to overcome immunotherapy resistance and summarizes the mechanisms and current status of related immunotherapeutic strategies. It also discusses the current bottlenecks and future directions of metabolism-targeted cancer immunotherapy. Overall, this review not only elucidates the mechanisms by which mitochondrial metabolic reprogramming drives tumor immune evasion but also provides a theoretical basis for optimizing metabolism-targeted immunotherapy.