肿瘤微环境中免疫细胞的代谢研究进展

doi:10.3969/j.issn.1674-8115.2022.08.018

上海交通大学学报（医学版） ›› 2022, Vol. 42 ›› Issue (8): 1122-1130.doi: 10.3969/j.issn.1674-8115.2022.08.018

肿瘤微环境中免疫细胞的代谢研究进展

林家俞(), 秦洁洁, 蒋玲曦()

上海交通大学医学院附属瑞金医院普外科胰腺疾病诊疗中心，上海交通大学医学院胰腺疾病研究所，上海 200025

收稿日期:2022-04-27 接受日期:2022-07-27 出版日期:2022-08-28 发布日期:2022-10-08
通讯作者: 蒋玲曦，电子信箱：jlx12120@rjh.com.cn。
作者简介:林家俞（1998—），男，硕士生；电子信箱：lam_ljy@163.com。
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

LIN Jiayu(), QIN Jiejie, JIANG Lingxi()

Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine; Research Institute of Pancreatic Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

Received:2022-04-27 Accepted:2022-07-27 Online:2022-08-28 Published:2022-10-08
Contact: JIANG Lingxi, E-mail: jlx12120@rjh.com.cn.
Supported by:
National Natural Science Foundation of China(82173219);Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support(20200037)

摘要/Abstract

摘要：

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。

关键词: 肿瘤微环境, 免疫细胞, 代谢途径, 免疫功能

Abstract:

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.

Key words: tumor microenvironment (TME), immune cell, metabolic pathway, immunity function

中图分类号:

R772.2

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.

LIN Jiayu, QIN Jiejie, JIANG Lingxi. Progress in metabolism of the immune cells in tumor microenvironment[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(8): 1122-1130.

图/表 2

参考文献 66

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Immunity type	Cell type	Metabolic pathway	Reference
Innate immunity
	M1-type TAMs	PPP	［12-13］
	M2-type TAMs	OXPHOS， FAO	［16-17］
	TANs	Glycolysis	［20］
	NKs	Glycolysis， OXPHOS	［23］
	DCs	Glycolysis	［27］
	MDSCs	Glycolysis， OXPHOS	［31］
Adaptive immunity
	Effector T cells	Glycolysis， lipid metabolism	［37，44］
	Tregs	Lipid metabolism， OXPHOS	［34］
	Effector B cells	Glycolysis， OXPHOS	［58-59］

Immunity type	Cell type	Metabolic pathway	Reference
Innate immunity
	M1-type TAMs	PPP	［12-13］
	M2-type TAMs	OXPHOS， FAO	［16-17］
	TANs	Glycolysis	［20］
	NKs	Glycolysis， OXPHOS	［23］
	DCs	Glycolysis	［27］
	MDSCs	Glycolysis， OXPHOS	［31］
Adaptive immunity
	Effector T cells	Glycolysis， lipid metabolism	［37，44］
	Tregs	Lipid metabolism， OXPHOS	［34］
	Effector B cells	Glycolysis， OXPHOS	［58-59］

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肿瘤微环境中免疫细胞的代谢研究进展

Progress in metabolism of the immune cells in tumor microenvironment

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