Metabolic Switch in the Tumor Microenvironment Determines Immune Responses to Anti-cancer Therapy

被引:73
|
作者
Wegiel, Barbara [1 ,2 ]
Vuerich, Marta [3 ]
Daneshmandi, Saeed [3 ]
Seth, Pankaj [2 ,3 ,4 ]
机构
[1] Beth Israel Deaconess Med Ctr, Dept Surg, 330 Brookline Ave, Boston, MA 02215 USA
[2] Beth Israel Deaconess Med Ctr, Canc Res Inst, Boston, MA 02215 USA
[3] Beth Israel Deaconess Med Ctr, Div Interdisciplinary Med, Boston, MA 02215 USA
[4] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA
来源
FRONTIERS IN ONCOLOGY | 2018年 / 8卷
关键词
tumor microenvironment (TME); metabolic reprogramming; immune stroma; HIF-1; alpha; lactate; FATTY-ACID OXIDATION; LACTATE DEHYDROGENASE-A; T-CELL METABOLISM; SUPPRESSOR-CELLS; CANCER-CELLS; P53-INDUCIBLE REGULATOR; COLONIC-MUCOSA; MYELOID CELLS; LUNG-CANCER; LACTIC-ACID;
D O I
10.3389/fonc.2018.00284
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Tumor-induced immune tolerance permits growth and spread of malignant cells. Cancer cells have strong influence on surrounding cells and shape the hypoxic tumor microenvironment (TME) facilitating cancer progression. A dynamic change in glucose metabolism occurring in cancer cells and its influence on the TME are still poorly understood. Indeed, cancer and/or immune cells undergo rapid adaptation in metabolic pathways during cancer progression. Metabolic reprograming affects macrophages, T cells, and myeloid derived suppressor cells (MDSCs) among other immune cells. Their role in the TME depends on a nature and concentration of factors, such as cytokines, reactive oxygen species (ROS), growth factors, and most importantly, diffusible metabolites (i.e., lactate). Further, the amounts of available nutrients and oxygen as well as activity of microbiota may influence metabolic pathways in the TME. The roles of metabolites in regulating of the interaction between immune and cancer cell are highlighted in this review. Targeting metabolic reprogramming or signaling pathways controlling cell metabolism in the TME might be a potential strategy for anti-cancer therapy alone or in combination with current immunotherapies.
引用
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页数:9
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