College of Life and Environmental Science, Wenzhou University, Zhejiang Provincial Key Laboratory for Water Environment and Marine Biological Resources Protection, Wenzhou 325035, Zhejiang Province, China.
Life Sciences Institute, Zhejiang University, Hangzhou 310058, China.
Zhejiang Da Xue Xue Bao Yi Xue Ban. 2024 Jan 5;53(1):1-14. doi: 10.3724/zdxbyxb-2023-0484.
Tumor cells adapt their metabolism to meet the demands for energy and biosynthesis. Mitochondria, pivotal organelles in the metabolic reprogramming of tumor cells, contribute to tumorigenesis and cancer progression significantly through various dysfunctions in both tumor and immune cells. Alterations in mitochondrial dynamics and metabolic signaling pathways exert crucial regulatory influence on the activation, proliferation, and differentiation of immune cells. The tumor microenvironment orchestrates the activation and functionality of tumor-infiltrating immune cells by reprogramming mitochondrial metabolism and inducing shifts in mitochondrial dynamics, thereby facilitating the establishment of a tumor immunosuppressive microenvironment. Stress-induced leakage of mitochondrial DNA contributes multifaceted regulatory effects on anti-tumor immune responses and the immunosuppressive microenvironment by activating multiple natural immune signals, including cGAS-STING, TLR9, and NLRP3. Moreover, mitochondrial DNA-mediated immunogenic cell death emerges as a promising avenue for anti-tumor immunotherapy. Additionally, mitochondrial reactive oxygen species, a crucial factor in tumorigenesis, drives the formation of tumor immunosuppressive microenvironment by changing the composition of immune cells within the tumor microenvironment. This review focuses on the intrinsic relationship between mitochondrial biology and anti-tumor immune responses from multiple angles. We explore the core role of mitochondria in the dynamic interplay between the tumor and the host to facilitate the development of targeted mitochondrial strategies for anti-tumor immunotherapy.
肿瘤细胞通过适应代谢来满足能量和生物合成的需求。线粒体是肿瘤细胞代谢重编程的关键细胞器，通过肿瘤细胞和免疫细胞的各种功能障碍，对肿瘤发生和癌症进展有重要贡献。线粒体动力学和代谢信号通路的改变对免疫细胞的激活、增殖和分化具有重要的调节作用。肿瘤微环境通过重编程线粒体代谢和诱导线粒体动力学的变化来协调肿瘤浸润免疫细胞的激活和功能，从而促进肿瘤免疫抑制微环境的建立。应激诱导的线粒体 DNA 漏出通过激活多个天然免疫信号，包括 cGAS-STING、TLR9 和 NLRP3，对抗肿瘤免疫反应和免疫抑制微环境产生多方面的调节作用。此外，线粒体 DNA 介导的免疫原性细胞死亡作为一种有前途的抗肿瘤免疫治疗方法出现。此外，肿瘤发生的关键因素——线粒体活性氧，通过改变肿瘤微环境中免疫细胞的组成，驱动肿瘤免疫抑制微环境的形成。本综述从多个角度关注线粒体生物学与抗肿瘤免疫反应之间的内在关系。我们探讨了线粒体在肿瘤与宿主动态相互作用中的核心作用，以促进针对抗肿瘤免疫治疗的靶向线粒体策略的发展。
