State Key Laboratory of Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China.
Department of Head and Neck Cancer Surgery, West China School of Stomatology, Sichuan University, Chengdu, China.
Cell Oncol (Dordr). 2023 Aug;46(4):847-865. doi: 10.1007/s13402-023-00801-0. Epub 2023 Apr 11.
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.
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.
癌症越来越被认为是一种代谢疾病,有证据表明氧化磷酸化(OXPHOS)在许多癌细胞的进展中起着重要作用。OXPHOS 不仅为肿瘤组织的存活提供足够的能量,还调节肿瘤增殖、侵袭和转移的条件。OXPHOS 的改变也会损害肿瘤微环境中免疫细胞的免疫功能,导致免疫逃逸。因此,研究 OXPHOS 与免疫逃逸之间的关系在癌症相关研究中至关重要。本综述旨在总结转录、线粒体遗传、代谢调节和线粒体动力学对不同癌症中 OXPHOS 的影响。此外,它还强调了 OXPHOS 通过影响各种免疫细胞在免疫逃逸中的作用。最后,通过分析现有靶向药物的局限性,对同时针对免疫和代谢过程的抗肿瘤策略的最新进展进行了概述,并提出了有前途的治疗靶点。
向 OXPHOS 的代谢转变对肿瘤的增殖、进展、转移、免疫逃逸和预后不良有重要贡献。深入研究不同类型肿瘤中 OXPHOS 调节的具体机制,并将 OXPHOS 靶向药物与现有的免疫疗法相结合,可能为未来的抗肿瘤治疗揭示新的治疗靶点。