Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida, Konoe-cho, Sakyo-ku, Kyoto, Japan.
Int Immunol. 2021 Jan 1;33(1):17-26. doi: 10.1093/intimm/dxaa046.
Energy metabolism plays an important role in proliferating cells. Recent reports indicate that metabolic regulation or metabolic products can control immune cell differentiation, fate and reactions. Cancer immunotherapy based on blockade of programmed cell death protein 1 (PD-1) has been used worldwide, but a significant fraction of patients remain unresponsive. Therefore, clarifying the mechanisms and overcoming the unresponsiveness are urgent issues. Because cancer immunity consists of interactions between the cancer and host immune cells, there has recently been a focus on the metabolic interactions and/or competition between the tumor and the immune system to address these issues. Cancer cells render their microenvironment immunosuppressive, driving T-cell dysfunction or exhaustion, which is advantageous for cancer cell survival. However, accumulating mechanistic evidence of T-cell and cancer cell metabolism has gradually revealed that controlling the metabolic pathways of either type of cell can overcome T-cell dysfunction and reprogram the metabolic balance in the tumor microenvironment. Here, we summarize the role of immune metabolism in T-cell-based immune surveillance and cancer immune escape. This new concept has boosted the development of combination therapy and predictive biomarkers in cancer immunotherapy with immune checkpoint inhibitors.
能量代谢在增殖细胞中起着重要作用。最近的报告表明，代谢调控或代谢产物可以控制免疫细胞的分化、命运和反应。基于程序性细胞死亡蛋白 1（PD-1）阻断的癌症免疫疗法已在全球范围内应用，但仍有相当一部分患者无反应。因此，阐明机制和克服无反应性是当务之急。由于癌症免疫由癌症和宿主免疫细胞之间的相互作用组成，最近人们关注肿瘤和免疫系统之间的代谢相互作用和/或竞争，以解决这些问题。癌细胞使它们的微环境免疫抑制，导致 T 细胞功能障碍或衰竭，这有利于癌细胞的存活。然而，越来越多的 T 细胞和癌细胞代谢的机制证据逐渐揭示，控制任何一种细胞的代谢途径都可以克服 T 细胞功能障碍，并重新编程肿瘤微环境中的代谢平衡。在这里，我们总结了免疫代谢在基于 T 细胞的免疫监视和癌症免疫逃逸中的作用。这一新概念促进了癌症免疫疗法中免疫检查点抑制剂联合治疗和预测生物标志物的发展。
