Crosstalk between oxidative phosphorylation and immune escape in cancer: a new concept of therapeutic targets selection

Abstract

Background: Cancer is increasingly recognized as a metabolic disease, with evidence suggesting that oxidative phosphorylation (OXPHOS) plays a significant role in the progression of numerous cancer cells. OXPHOS not only provides sufficient energy for tumor tissue survival but also regulates conditions for tumor proliferation, invasion, and metastasis. Alterations in OXPHOS can also impair the immune function of immune cells in the tumor microenvironment, leading to immune evasion. Therefore, investigating the relationship between OXPHOS and immune escape is crucial in cancer-related research. This review aims to summarize the effects of transcriptional, mitochondrial genetic, metabolic regulation, and mitochondrial dynamics on OXPHOS in different cancers. Additionally, it highlights the role of OXPHOS in immune escape by affecting various immune cells. Finally, it concludes with an overview of recent advances in antitumor strategies targeting both immune and metabolic processes and proposes promising therapeutic targets by analyzing the limitations of current targeted drugs.

Conclusions: The metabolic shift towards OXPHOS contributes significantly to tumor proliferation, progression, metastasis, immune escape, and poor prognosis. A thorough investigation of concrete mechanisms of OXPHOS regulation in different types of tumors and the combination usage of OXPHOS-targeted drugs with existing immunotherapies could potentially uncover new therapeutic targets for future antitumor therapies.

Keywords: Cancer therapy; Immunotherapy; Metabolism; OXPHOS.