Translational Tumor Immunology Group, Ludwig Cancer Research, University of Lausanne, Lausanne, Switzerland; Department of Fundamental Oncology, University of Lausanne, Lausanne, Switzerland.
Trends Mol Med. 2018 Jan;24(1):30-48. doi: 10.1016/j.molmed.2017.11.005. Epub 2017 Dec 12.
CD8 T cells are central players in controlling infections and cancer. Longevity, functionality, and metabolic fitness are critical determinants of T cell efficacy in cancer immunotherapy. Tumor-infiltrating CD8 T cells undergo metabolic 'exhaustion' in the nutrient- and oxygen-deprived tumor microenvironment (TME). Thus, reprograming CD8 T cell metabolism may provide important therapeutic strategies for cancer treatment. Indeed, the adoptive transfer of memory CD8 T cells with sustained metabolic fitness may yield better antitumor protection in both mouse models and the clinic. Here, we discuss recent progress on how cellular metabolism is linked to CD8 T cell fate decisions and on how metabolic intermediates can impact gene expression via modulation of the epigenome. We examine the feasibility of developing potential strategies to improve antitumor immunity through the modulation of T cell metabolic activity.
CD8 T 细胞是控制感染和癌症的核心参与者。在癌症免疫疗法中，T 细胞的寿命、功能和代谢健康是其疗效的关键决定因素。浸润肿瘤的 CD8 T 细胞在营养和氧气匮乏的肿瘤微环境（TME）中经历代谢“衰竭”。因此，重新编程 CD8 T 细胞代谢可能为癌症治疗提供重要的治疗策略。事实上，在小鼠模型和临床中，过继转移具有持续代谢健康的记忆 CD8 T 细胞可能会产生更好的抗肿瘤保护作用。在这里，我们讨论了细胞代谢如何与 CD8 T 细胞命运决定相关，以及代谢中间产物如何通过调节表观基因组来影响基因表达的最新进展。我们研究了通过调节 T 细胞代谢活性来提高抗肿瘤免疫力的潜在策略的可行性。
