The broad effectiveness of T cell-based therapy for treating solid tumour cancers remains limited. This is partly due to the growing appreciation that immune cells must inhabit and traverse a metabolically demanding tumour environment. Accordingly, recent efforts have centred on using genome-editing technologies to augment T cell-mediated cytotoxicity by manipulating specific metabolic genes. However, solid tumours exhibit numerous characteristics restricting immune cell-mediated cytotoxicity, implying a need for metabolic engineering at the pathway level rather than single gene targets. This emerging concept has yet to be put into clinical practice as many questions concerning the complex interplay between metabolic networks and T cell function remain unsolved. This Perspective will highlight key foundational studies that examine the relevant metabolic pathways required for effective T cell cytotoxicity and persistence in the human tumour microenvironment, feasible strategies for metabolic engineering to increase the efficiency of chimeric antigen receptor T cell-based approaches, and the challenges lying ahead for clinical implementation.

基于 T 细胞的疗法治疗实体瘤的广泛有效性仍然有限。部分原因是人们越来越认识到免疫细胞必须栖息并穿越代谢要求较高的肿瘤环境。因此，最近的努力集中在使用基因组编辑技术通过操纵特定的代谢基因来增强 T 细胞介导的细胞毒性。然而，实体瘤表现出许多限制免疫细胞介导的细胞毒性的特征，这意味着需要在途径水平而不是单基因靶点进行代谢工程。这一新兴概念尚未投入临床实践，因为有关代谢网络和 T 细胞功能之间复杂相互作用的许多问题仍未解决。本视角将重点介绍关键的基础研究，这些研究检查有效 T 细胞细胞毒性和在人类肿瘤微环境中持续存在所需的相关代谢途径、提高嵌合抗原受体 T 细胞方法效率的代谢工程可行策略，以及面临的挑战提前临床实施。