Metabolites as agents and targets for cancer immunotherapy

Marcel P. Trefny, Guido Kroemer, Laurence Zitvogel, Sebastian Kobold
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Abstract

The depletion or accumulation of metabolites in the tumour microenvironment is one of the hallmarks of cancer, but targeting cancer cell metabolism therapeutically must also take into account the impact on metabolic pathways in immune cells. As we understand more about immunometabolism, opportunities arise for synergies between agents that modulate metabolism and immunotherapy. In this Review, we discuss the pivotal role of metabolic pathways in both cancer and immune cells in shaping the tumour microenvironment. We survey major anabolic and catabolic pathways and discuss how metabolic modulators and dietary nutrients can improve the anticancer immune response and overcome drug resistance mechanisms. Agents in the clinic include inhibitors of the adenosine and tryptophan pathways, and we discuss opportunities and challenges for successful drug development in the context of immune checkpoint blockade and chimeric antigen receptor (CAR)-T cell therapies.

Abstract Image

代谢物作为肿瘤免疫治疗的药物和靶点
肿瘤微环境中代谢物的消耗或积累是癌症的标志之一,但靶向癌细胞代谢治疗也必须考虑到对免疫细胞代谢途径的影响。随着我们对免疫代谢的了解越来越多,在调节代谢和免疫治疗的药物之间产生协同作用的机会就越来越多。在这篇综述中,我们讨论了癌症和免疫细胞代谢途径在塑造肿瘤微环境中的关键作用。我们调查了主要的合成代谢和分解代谢途径,并讨论了代谢调节剂和膳食营养素如何提高抗癌免疫反应和克服耐药机制。临床上的药物包括腺苷和色氨酸途径的抑制剂,我们讨论了在免疫检查点阻断和嵌合抗原受体(CAR)-T细胞疗法的背景下成功开发药物的机遇和挑战。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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