Vanderbilt Center for Immunobiology, Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee.
Cancer Discov. 2021 Jul;11(7):1636-1643. doi: 10.1158/2159-8290.CD-20-0569. Epub 2021 Apr 1.
Immune oncology approaches of adoptive cell therapy and immune checkpoint blockade aim to activate T cells to eliminate tumors. Normal stimulation of resting T cells induces metabolic reprogramming from catabolic and oxidative metabolism to aerobic glycolysis in effector T cells, and back to oxidative metabolism in long-lived memory cells. These metabolic reprogramming events are now appreciated to be essential aspects of T-cell function and fate. Here, we review these transitions, how they are disrupted by T-cell interactions with tumors and the tumor microenvironment, and how they can inform immune oncology to enhance T-cell function against tumors. SIGNIFICANCE: T-cell metabolism plays a central role in T-cell fate yet is altered in cancer in ways that can suppress antitumor immunity. Here, we discuss challenges and opportunities to stimulate effector T-cell metabolism and improve cancer immunotherapy.
免疫肿瘤学的过继细胞疗法和免疫检查点阻断方法旨在激活 T 细胞以消除肿瘤。静息 T 细胞的正常刺激会诱导效应 T 细胞从分解代谢和氧化代谢向有氧糖酵解转变，然后在长寿记忆细胞中再向氧化代谢转变。现在人们认识到，这些代谢重编程事件是 T 细胞功能和命运的重要方面。在这里，我们回顾了这些转变，以及它们如何被 T 细胞与肿瘤和肿瘤微环境的相互作用所破坏，以及它们如何为免疫肿瘤学提供信息，以增强 T 细胞对抗肿瘤的功能。意义：T 细胞代谢在 T 细胞命运中起着核心作用，但在癌症中会以抑制抗肿瘤免疫的方式发生改变。在这里，我们讨论了刺激效应 T 细胞代谢和改善癌症免疫治疗的挑战和机遇。
