In the direct competition for metabolic resources between cancer cells and tumor-infiltrating CD8⁺ T cells, the latter are bound to lose out. These effector lymphocytes are therefore rendered exhausted or dysfunctional. Emerging insights into the mechanisms of T cell unresponsiveness in the tumor microenvironment (TME) point towards epigenetic mechanisms as crucial regulatory factors. In this review, we discuss the effects of characteristic components of the TME, i.e. glucose/amino acid dearth with elevated levels of reactive oxygen species (ROS), on DNA methylation and histone modifications in CD8⁺ T cells. We then take a closer look at the translational potential of epigenetic interventions that aim to improve current immunotherapeutic strategies, including the adoptive transfer of T cell receptor (TCR) or chimeric antigen receptor (CAR) engineered T cells.

在癌细胞与肿瘤浸润性CD8 ⁺ T细胞对代谢资源的直接竞争中，后者势必落败。这些效应淋巴细胞因此变得耗尽或功能失调。对肿瘤微环境 (TME) 中 T 细胞无反应机制的新见解指向表观遗传机制作为关键调节因素。在这篇综述中，我们讨论了 TME 的特征成分（即葡萄糖/氨基酸缺乏和活性氧 (ROS) 水平升高）对 CD8 ^{+中 DNA 甲基化和组蛋白修饰的影响}T 细胞。然后，我们仔细研究旨在改善当前免疫治疗策略的表观遗传干预的转化潜力，包括 T 细胞受体 (TCR) 或嵌合抗原受体 (CAR) 工程化 T 细胞的过继转移。