The immune system shapes tumor development and progression. Although immunotherapy has transformed cancer treatment, its overall efficacy remains limited, underscoring the need to uncover mechanisms to improve therapeutic effects. Metabolism-associated processes, including intracellular metabolic reprogramming and intercellular metabolic crosstalk, are emerging as instructive signals for anti-tumor immunity. Here, we first summarize the roles of intracellular metabolic pathways in controlling immune cell function in the tumor microenvironment. How intercellular metabolic communication regulates anti-tumor immunity, and the impact of metabolites or nutrients on signaling events, are also discussed. We then describe how targeting metabolic pathways in tumor cells or intratumoral immune cells or via nutrient-based interventions may boost cancer immunotherapies. Finally, we conclude with discussions on profiling and functional perturbation methods of metabolic activity in intratumoral immune cells, and perspectives on future directions. Uncovering the mechanisms for metabolic rewiring and communication in the tumor microenvironment may enable development of novel cancer immunotherapies.

免疫系统决定肿瘤的发展和进展。尽管免疫疗法已经改变了癌症治疗，但其总体疗效仍然有限，这凸显了需要揭示改善治疗效果的机制。代谢相关过程，包括细胞内代谢重编程和细胞间代谢串扰，正在成为抗肿瘤免疫的指导信号。在这里，我们首先总结了细胞内代谢途径在控制肿瘤微环境中免疫细胞功能中的作用。还讨论了细胞间代谢通讯如何调节抗肿瘤免疫，以及代谢物或营养物质对信号事件的影响。然后，我们描述了如何针对肿瘤细胞或瘤内免疫细胞中的代谢途径或通过基于营养的干预措施来促进癌症免疫疗法。最后，我们讨论了瘤内免疫细胞代谢活动的分析和功能扰动方法，并对未来方向进行了展望。揭示肿瘤微环境中代谢重连和通讯的机制可能有助于开发新型癌症免疫疗法。