Cai Qiaoting, Deng Wei, Zou Yutian, Chen Zhe-Sheng, Tang Hailin
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
College of Pharmacy and Health Sciences, St. John's University, Queens, NY, USA.
Med Rev (2021). 2024 Dec 17;5(3):256-259. doi: 10.1515/mr-2024-0091. eCollection 2025 Jun.
Lactate is the end product of glycolysis, and extensive research has shown that lactate participates in various pathophysiological processes. Along with associated hydrogen ions, lactate typically functions as an immunosuppressive negative factor and plays a crucial role in tumor metabolic reprogramming. The recently discovered lactylation is a novel epigenetic modification that, similar to other epigenetic modifications, modifies histones to alter chromatin spatial configuration, thereby affecting DNA accessibility and regulating gene expression. More importantly, the degree of lactylation is closely related to local lactate concentrations, establishing a link between epigenetics and metabolic reprogramming. During cellular metabolism, lactate accumulation promotes histone lysine lactylation in cancer cells and immune cells such as macrophages and T cells, playing an essential role in tumor immune evasion and resistance to immunotherapy. This paper details the role of lactylation modifications in cancer immune evasion and resistance to immunotherapy, providing novel therapeutic directions and targets for cancer treatment.
乳酸是糖酵解的终产物，大量研究表明乳酸参与多种病理生理过程。与相关氢离子一起，乳酸通常作为一种免疫抑制负性因子发挥作用，并在肿瘤代谢重编程中起关键作用。最近发现的乳酸化是一种新的表观遗传修饰，与其他表观遗传修饰类似，它修饰组蛋白以改变染色质空间构型，从而影响DNA可及性并调节基因表达。更重要的是，乳酸化程度与局部乳酸浓度密切相关，建立了表观遗传学与代谢重编程之间的联系。在细胞代谢过程中，乳酸积累促进癌细胞以及巨噬细胞和T细胞等免疫细胞中的组蛋白赖氨酸乳酸化，在肿瘤免疫逃逸和免疫治疗抗性中起重要作用。本文详细阐述了乳酸化修饰在癌症免疫逃逸和免疫治疗抗性中的作用，为癌症治疗提供了新的治疗方向和靶点。
