Chimeric antigen receptor (CAR) T cells have achieved true clinical success in treating hematological malignancy patients, laying the foundation of CAR T cells as a new pillar of cancer therapy. Although these promising effects have generated strong interest in expanding the treatment of CAR T cells to solid tumors, reproducible demonstration of clinical efficacy in the setting of solid tumors has remained challenging to date. Here, we review how metabolic stress and signaling in the tumor microenvironment, including intrinsic determinants of response to CAR T cell therapy and extrinsic obstacles, restrict the efficacy of CAR T cell therapy in cancer treatment. In addition, we discuss the use of novel approaches to target and rewire metabolic programming for CAR T cell manufacturing. Last, we summarize strategies that aim to improve the metabolic adaptability of CAR T cells to enhance their potency in mounting antitumor responses and survival within the tumor microenvironment.

中文翻译：

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CAR T 细胞疗法中的代谢挑战和干预措施

嵌合抗原受体（CAR）T细胞在治疗血液系统恶性肿瘤患者方面取得了真正的临床成功，奠定了CAR T细胞作为癌症治疗新支柱的基础。尽管这些有前途的效果引起了人们对将 CAR T 细胞的治疗扩展到实体瘤的强烈兴趣，但迄今为止，在实体瘤中临床疗效的可重复性证明仍然具有挑战性。在这里，我们回顾了肿瘤微环境中的代谢应激和信号传导，包括对 CAR T 细胞疗法反应的内在决定因素和外在障碍，如何限制 CAR T 细胞疗法在癌症治疗中的疗效。此外，我们还讨论了使用新方法来靶向和重新连接 CAR T 细胞制造的代谢编程。最后的，