Clay Ryan, Li Kunyang, Jin Lingtao
Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Cancers (Basel). 2025 Jan 6;17(1):155. doi: 10.3390/cancers17010155.
Cancer cells must reprogram their metabolism to sustain rapid growth. This is accomplished in part by switching to aerobic glycolysis, uncoupling glucose from mitochondrial metabolism, and performing anaplerosis via alternative carbon sources to replenish intermediates of the tricarboxylic acid (TCA) cycle and sustain oxidative phosphorylation (OXPHOS). While this metabolic program produces adequate biosynthetic intermediates, reducing agents, ATP, and epigenetic remodeling cofactors necessary to sustain growth, it also produces large amounts of byproducts that can generate a hostile tumor microenvironment (TME) characterized by low pH, redox stress, and poor oxygenation. In recent years, the focus of cancer metabolic research has shifted from the regulation and utilization of cancer cell-intrinsic pathways to studying how the metabolic landscape of the tumor affects the anti-tumor immune response. Recent discoveries point to the role that secreted metabolites within the TME play in crosstalk between tumor cell types to promote tumorigenesis and hinder the anti-tumor immune response. In this review, we will explore how crosstalk between metabolites of cancer cells, immune cells, and stromal cells drives tumorigenesis and what effects the competition for resources and metabolic crosstalk has on immune cell function.
癌细胞必须重新编程其代谢以维持快速生长。这部分是通过转向有氧糖酵解、使葡萄糖与线粒体代谢解偶联以及通过替代碳源进行回补反应来补充三羧酸（TCA）循环的中间产物并维持氧化磷酸化（OXPHOS）来实现的。虽然这种代谢程序产生了维持生长所需的足够的生物合成中间体、还原剂、ATP和表观遗传重塑辅因子，但它也产生了大量副产物，这些副产物会产生以低pH值、氧化还原应激和低氧化为特征的恶劣肿瘤微环境（TME）。近年来，癌症代谢研究的重点已从癌细胞内在途径的调节和利用转向研究肿瘤的代谢格局如何影响抗肿瘤免疫反应。最近的发现指出了肿瘤微环境中分泌的代谢物在肿瘤细胞类型之间的串扰中所起的作用，以促进肿瘤发生并阻碍抗肿瘤免疫反应。在这篇综述中，我们将探讨癌细胞、免疫细胞和基质细胞的代谢物之间的串扰如何驱动肿瘤发生，以及资源竞争和代谢串扰对免疫细胞功能有何影响。
