Metabolic gatekeepers: harnessing tumor-derived metabolites to optimize T cell-based immunotherapy efficacy in the tumor microenvironment.

IF 8.1 1区生物学 Q1 CELL BIOLOGY Cell Death & Disease Pub Date : 2024-10-26 DOI:10.1038/s41419-024-07122-6

Yucheng Zheng, Rongwei Xu, Xu Chen, Ye Lu, Jiarong Zheng, Yunfan Lin, Pei Lin, Xinyuan Zhao, Li Cui

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Abstract

The tumor microenvironment (TME) orchestrates a complex interplay between tumor cells and immune cells, crucially modulating the immune response. This review delves into the pivotal role of metabolic reprogramming in the TME, highlighting how tumor-derived metabolites influence T lymphocyte functionality and the efficacy of cancer immunotherapies. Focusing on the diverse roles of these metabolites, we examine how lactate, lipids, amino acids, and other biochemical signals act not only as metabolic byproducts but as regulatory agents that can suppress or potentiate T cell-mediated immunity. By integrating recent findings, we underscore the dual impact of these metabolites on enhancing tumor progression and inhibiting immune surveillance. Furthermore, we propose innovative therapeutic strategies that target metabolic pathways to restore immune function within the TME. The insights provided in this review pave the way for the development of metabolic interventions aimed at enhancing the success of immunotherapies in oncology, offering new hope for precision medicine in the treatment of cancer.

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代谢守门员：利用肿瘤衍生代谢物优化肿瘤微环境中基于 T 细胞的免疫疗法疗效。

肿瘤微环境（TME）协调着肿瘤细胞和免疫细胞之间复杂的相互作用，对免疫反应起着至关重要的调节作用。这篇综述深入探讨了代谢重编程在肿瘤微环境中的关键作用，强调了肿瘤衍生代谢物如何影响 T 淋巴细胞的功能和癌症免疫疗法的疗效。我们将重点放在这些代谢物的不同作用上，研究乳酸、脂类、氨基酸和其他生化信号如何不仅作为代谢副产物，而且作为调节剂抑制或增强 T 细胞介导的免疫力。通过整合最新研究成果，我们强调了这些代谢物在促进肿瘤进展和抑制免疫监视方面的双重影响。此外，我们还提出了针对代谢途径的创新治疗策略，以恢复 TME 内的免疫功能。本综述提供的见解为开发旨在提高肿瘤免疫疗法成功率的代谢干预措施铺平了道路，为精准医学治疗癌症带来了新的希望。

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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来源期刊

Cell Death & Disease CELL BIOLOGY-

CiteScore

15.10

自引率

2.20%

发文量

935

审稿时长

2 months

期刊介绍： Brought to readers by the editorial team of Cell Death & Differentiation, Cell Death & Disease is an online peer-reviewed journal specializing in translational cell death research. It covers a wide range of topics in experimental and internal medicine, including cancer, immunity, neuroscience, and now cancer metabolism. Cell Death & Disease seeks to encompass the breadth of translational implications of cell death, and topics of particular concentration will include, but are not limited to, the following: Experimental medicine Cancer Immunity Internal medicine Neuroscience Cancer metabolism