收稿日期: 2022-04-27
录用日期: 2022-07-27
网络出版日期: 2022-10-08
基金资助
国家自然科学基金面上项目(82173219);上海市教育委员会高峰高原学科建设计划(20200037)
Progress in metabolism of the immune cells in tumor microenvironment
Received date: 2022-04-27
Accepted date: 2022-07-27
Online published: 2022-10-08
Supported by
National Natural Science Foundation of China(82173219);Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support(20200037)
代谢重编程是细胞为满足能量需求，通过改变代谢模式来促进细胞增殖和生长的机制。肿瘤细胞通过Warburg效应等代谢重编程模式来供能，以促进自身的生存、生长与转移。肿瘤微环境即肿瘤细胞自身所处的内环境，其不仅包括肿瘤细胞本身，还包括与肿瘤细胞关系密切的基质细胞、免疫细胞等组分。肿瘤细胞通过分泌细胞因子、代谢产物等生化分子调控细胞之间的免疫功能、信号转导，并塑造一个缺氧、酸性、营养物质匮乏的肿瘤微环境，阻断免疫细胞的抗肿瘤效应。快速增殖的肿瘤细胞与免疫细胞竞争相对匮乏的营养物质，使得肿瘤细胞本身就可营造一种免疫抑制的微环境。在免疫抑制的肿瘤微环境影响下，免疫细胞通过代谢重编程的方式来产生耐受表型相关的代谢适应，以满足自身需求，并发挥抗肿瘤或免疫抑制的功能。免疫细胞对肿瘤细胞的反应主要依赖于其特有的代谢途径，这与免疫细胞的类型与功能有关。免疫细胞的功能特性与肿瘤的免疫治疗效果直接相关。调节免疫细胞的代谢途径，可为肿瘤治疗提供良好的方向。该文阐述肿瘤微环境中免疫细胞的主要代谢途径，总结其代谢特征与免疫功能的关系，讨论代谢通路调节免疫细胞功能的作用机制，以期为改造肿瘤免疫抑制微环境及改善肿瘤免疫治疗效果提供新的思路。
林家俞 , 秦洁洁 , 蒋玲曦 . 肿瘤微环境中免疫细胞的代谢研究进展[J]. 上海交通大学学报（医学版）, 2022 , 42(8) : 1122 -1130 . DOI: 10.3969/j.issn.1674-8115.2022.08.018
Metabolic reprogramming refers to cells' mechanism to change their metabolic patterns in order to meet the increased energy demand caused by growth and proliferation. By way of metabolic reprogramming such as the Warburg effect, tumor cells gain rich energy to support their own survival, growth, and metastasis. The tumor microenvironment (TME) is the internal environment in which tumor cells survive, containing not only tumor cells, but also stromal cells, immune cells, and other components that are closely related to tumor cells. Meanwhile, tumor cells regulate intercellular function and signaling via secreting cytokines, metabolites, and other molecules and shape a commonly hypoxic, acidic, and nutrient-deprived TME which contributes the most to immune resistance. However, rapidly proliferating tumor cells compete for relatively scarce nutrients with immune cells, consequently, producing an immunosuppressive metabolism microenvironment. Under the influence of immunosuppressive TME, immune cells generate tolerance phenotype-related metabolic adaptations through metabolic reprogramming to satisfy their own needs and further perform anti-tumor or immunosuppressive roles. The response of immune cells to tumor cells mainly depends on respective unique metabolic pathways, which are related to the type and function of immune cells. Moreover, the functional properties of immune cells are directly associated with the immunotherapy effects. Regulating metabolic pathways of immune cells provides a great direction for cancer therapy. In this paper, the main metabolic pathways of immune cells in TME is described, the relationship between their metabolic characteristics and immune functions is summarized, and the mechanism of metabolic pathways underlying the functions of immune cells is further discussed, providing new insights for unveiling tumor immunosuppressive microenvironment and improving the efficacy of tumor immunotherapy.
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