Immunotherapy shifted the paradigm of cancer treatment. The clinical approval of immune checkpoint blockade and adoptive cell transfer led to considerable success in several tumor types. However, for a significant number of patients, these therapies have proven ineffective. Growing evidence shows that the metabolic requirements of immune cells in the tumor microenvironment (TME) greatly influence the success of immunotherapy. It is well established that the TME influences energy consumption and metabolic reprogramming of immune cells, often inducing them to become tolerogenic and inefficient in cancer cell eradication. Increasing nutrient availability using pharmacological modulators of metabolism or antibodies targeting specific immune receptors are strategies that support energetic rewiring of immune cells and boost their anti-tumor capacity. In this review, we describe the metabolic features of the diverse immune cell types in the context of the TME and discuss how these immunomodulatory strategies could synergize with immunotherapy to circumvent its current limitations.

免疫疗法改变了癌症治疗的范式。免疫检查点阻滞和过继性细胞转移的临床批准在多种肿瘤类型中取得了相当大的成功。然而，对于大量患者而言，这些疗法已被证明是无效的。越来越多的证据表明，肿瘤微环境（TME）中免疫细胞的代谢需求极大地影响了免疫治疗的成功。众所周知，TME会影响免疫细胞的能量消耗和代谢重编程，通常会导致它们在消除癌细胞方面变得耐受力低下。使用新陈代谢的药理学调节剂或靶向特定免疫受体的抗体来增加养分利用率是支持免疫细胞高能重新连接并增强其抗肿瘤能力的策略。