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乳酸对肿瘤微环境内免疫细胞的影响及相关靶点治疗的研究进展

Effect of Lactate on Immune Cells in Tumor Microenvironment and Progress of Related Target Therapy

  • 摘要: 肿瘤代谢与肿瘤免疫关系复杂多样,同时肿瘤细胞代谢重编程塑造特异性的肿瘤微环境,其在肿瘤免疫治疗方面的作用尚未解释清楚。乳酸是糖酵解的主要产物,肿瘤细胞的有氧糖酵解使乳酸在微环境内堆积。近年来,大量研究表明,肿瘤微环境内堆积的乳酸对抗肿瘤免疫造成阻碍,尤其影响了免疫细胞的功能、分化和代谢以及参与肿瘤免疫逃逸等,发挥着促肿瘤作用。本文回顾了肿瘤微环境内乳酸堆积对树突状细胞、T细胞、NK细胞、肿瘤相关巨噬细胞及髓源性抑制细胞的影响。靶向干预肿瘤细胞产生及外排乳酸的过程有望成为肿瘤免疫治疗的新策略。

     

    Abstract: The relationship between tumor metabolism and immunity is complex and diverse. To date, the role of tumor-specific metabolic reprogramming in shaping the specific tumor microenvironment in tumor immunotherapy remains unclear. Lactic acid is the main product of glycolysis, and the aerobic glycolysis of tumor cells causes lactic acid to accumulate in the microenvironment. Recent studies have shown that the accumulation of lactic acid in the tumor microenvironment hinders anti-tumor immunity, especially affects the function, differentiation, and metabolism of immune cells, and participates in tumor immune escape, thus promoting tumor. This article reviews the effects of lactate accumulation in the tumor microenvironment on dendritic cells, T cells, NK cells, tumor-associated macrophages, and myeloid-derived suppressor cells. Targeted intervention of lactate production and efflux by tumor cells is expected to become a new strategy for tumor immunotherapy.

     

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