乳酸化修饰在肿瘤免疫逃逸中的研究进展

Research progress on the role of lactylation in tumor immune evasion

摘要:

乳酸化修饰作为一种新型的翻译后修饰机制，近年来在肿瘤免疫逃逸中的作用日益受到关注。乳酸化修饰可分为组蛋白乳酸化和非组蛋白乳酸化两种类型，通过多种机制促进肿瘤免疫逃逸：包括影响免疫细胞的代谢重编程、促进巨噬细胞极化、调节免疫细胞的代谢与功能，以及调节免疫细胞的信号通路等。在免疫治疗方面，乳酸化修饰与PD-1抑制剂和CAR-T细胞疗法的耐药性密切相关，而靶向乳酸脱氢酶或特异性乳酸化位点可显著增强免疫治疗效果。该文探讨了乳酸化修饰与其他翻译后修饰的交互作用，以及靶向乳酸化修饰作为肿瘤免疫治疗新策略的潜在应用前景，为深入理解肿瘤免疫逃逸机制提供了新视角，并为开发新型免疫治疗策略提供了理论依据。?

Abstract:

Lactylation, as a novel post-translational modification mechanism, has increasingly attracted attention for its role in tumor immune evasion in recent years. Lactylation can be classified into histone and non-histone lactylation. It promotes tumor immune evasion through multiple mechanisms, including metabolic reprogramming of immune cells, promotion of macrophage polarization, regulation of immune cell metabolism and function, and modulation of immune cell signaling pathways. In the context of immunotherapy, lactylation is closely associated with resistance to PD-1 inhibitors and CAR-T cell therapy. Targeting lactate dehydrogenase or specific lactylation sites can significantly enhance the efficacy of immunotherapeutic interventions. This review explores the interplay between lactylation and other post-translational modifications, as well as the potential application prospects of targeting lactylation as a new strategy for tumor immunotherapy. These findings provide a novel perspective for a deeper understanding of the mechanisms of tumor immune evasion and offer a theoretical basis for the development of innovative immunotherapeutic approaches.