Coleman Michael F, Cozzo Alyssa J, Pfeil Alexander J, Etigunta Suhas K, Hursting Stephen D
Department of Nutrition, University of North Carolina, Chapel Hill, NC 27516, USA.
Department of Medicine, Duke University, Durham, NC 27705, USA.
Cancers (Basel). 2020 Apr 1;12(4):852. doi: 10.3390/cancers12040852.
Immune checkpoint inhibitor (ICI) therapy has shown extraordinary promise at treating cancers otherwise resistant to treatment. However, for ICI therapy to be effective, it must overcome the metabolic limitations of the tumor microenvironment. Tumor metabolism has long been understood to be highly dysregulated, with potent immunosuppressive effects. Moreover, T cell activation and longevity within the tumor microenvironment are intimately tied to T cell metabolism and are required for the long-term efficacy of ICI therapy. We discuss in this review the intersection of metabolic competition in the tumor microenvironment, T cell activation and metabolism, the roles of tumor cell metabolism in immune evasion, and the impact of host metabolism in determining immune surveillance and ICI therapy outcomes. We also discussed the effects of obesity and calorie restriction-two important systemic metabolic perturbations that impact intrinsic metabolic pathways in T cells as well as cancer cells.
免疫检查点抑制剂（ICI）疗法在治疗原本对治疗有抗性的癌症方面显示出非凡的前景。然而，要使ICI疗法有效，它必须克服肿瘤微环境的代谢限制。长期以来，人们一直认为肿瘤代谢高度失调，具有强大的免疫抑制作用。此外，肿瘤微环境中T细胞的激活和寿命与T细胞代谢密切相关，并且是ICI疗法长期疗效所必需的。在本综述中，我们讨论了肿瘤微环境中的代谢竞争、T细胞激活与代谢、肿瘤细胞代谢在免疫逃逸中的作用以及宿主代谢对免疫监视和ICI治疗结果的影响之间的交叉点。我们还讨论了肥胖和卡路里限制这两种重要的全身代谢扰动对T细胞以及癌细胞内在代谢途径的影响。
