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。这一过程部分通过转向有氧糖酵解实现，即将葡萄糖与线粒体代谢解耦，并通过替代碳源进行回补反应，以补充三羧酸（TCA）循环中间产物并维持氧化磷酸化（OXPHOS）。尽管这种代谢程序能产生足够的生物合成中间体、还原剂、ATP以及维持生长所需的表观遗传重塑辅因子，但同时也会产生大量副产物，这些副产物可形成具有低pH值、氧化还原应激和低氧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通路的调控与利用，转向研究肿瘤的代谢环境如何影响抗肿瘤免疫反应。最新发现揭示了TME中分泌代谢物在肿瘤细胞类型间相互作用中扮演的角色——它们既能促进肿瘤发生，又会阻碍抗肿瘤免疫反应。本综述将探讨癌细胞、免疫细胞和基质细胞的代谢物如何通过相互作用驱动肿瘤发生，以及资源竞争和代谢互作对免疫细胞功能产生的影响。
肿瘤(癌症)患者之家