Recent advances in immunotherapies such as immune checkpoint blockade (ICB) and chimeric antigen receptor T cells (CAR-T) for the treatment of cancer have generated excitement over their ability to yield durable, and potentially curative, responses in a multitude of cancers. These findings have established that the immune system is capable of eliminating tumors and led us to a better, albeit still incomplete, understanding of the mechanisms by which tumors interact with and evade destruction by the immune system. Given the central role of T cells in immunotherapy, elucidating the cell intrinsic and extrinsic factors that govern T cell function in tumors will facilitate the development of immunotherapies that establish durable responses in a greater number of patients. One such factor is metabolism, a set of fundamental cellular processes that not only sustains cell survival and proliferation, but also serves as a means for cells to interpret their local environment. Nutrient sensing is critical for T cells that must infiltrate into a metabolically challenging tumor microenvironment and expand under these harsh conditions to eliminate cancerous cells. Here we introduce T cell exhaustion with respect to cellular metabolism, followed by a discussion of nutrient availability at the tumor and organismal level in relation to T cell metabolism and function to provide rationale for the study and targeting of metabolism in anti-tumor immune responses.

用于治疗癌症的免疫检查点阻断 (ICB) 和嵌合抗原受体 T 细胞 (CAR-T) 等免疫疗法的最新进展，因其在多种癌症中产生持久且潜在治愈性反应的能力而令人兴奋。这些发现证实免疫系统能够消除肿瘤，并使我们对肿瘤与免疫系统相互作用并逃避免疫系统破坏的机制有了更好的了解，尽管仍然不完整。鉴于 T 细胞在免疫治疗中的核心作用，阐明控制肿瘤中 T 细胞功能的细胞内在和外在因素将有助于免疫疗法的发展，从而在更多患者中建立持久的反应。其中一个因素是新陈代谢，这是一组基本的细胞过程，不仅维持细胞生存和增殖，而且还是细胞解释其局部环境的一种手段。营养感应对于 T 细胞至关重要，T 细胞必须渗透到具有代谢挑战性的肿瘤微环境中，并在这些恶劣条件下进行扩增以消除癌细胞。在这里，我们介绍了与细胞代谢相关的 T 细胞耗竭，然后讨论了与 T 细胞代谢和功能相关的肿瘤和生物体水平的营养可用性，为抗肿瘤免疫反应中代谢的研究和靶向提供理论基础。