乳酸在肿瘤恶性进展中的作用:从代谢重编程到免疫微环境调控

The role of lactic acid in tumor malignant progression: from metabolic reprogramming to immune microenvironment regulation

摘要

恶性肿瘤研究中,乳酸已从单纯的代谢副产物转变为肿瘤进展的关键调控因子。本综述旨在阐明乳酸通过代谢重编程和免疫微环境调控双重机制影响肿瘤发展。肿瘤细胞经Warburg效应产生大量乳酸,其不仅作为能量底物支持肿瘤生长,还能主动调节代谢通路。乳酸累积形成的酸性微环境可重塑细胞外基质。在肿瘤免疫微环境中,酸化环境抑制T细胞活性;乳酸化修饰影响基因表达,利于肿瘤免疫逃逸,其通过激活受体传导信号,影响免疫细胞功能。2种机制协同促进血管生成和肿瘤侵袭转移。基于此,靶向LDHA、乳酸化修饰及相关受体的策略为肿瘤治疗带来希望。本综述构建的乳酸作用体系框架,为肿瘤代谢免疫治疗提供了新思路。

Abstract

In malignant tumor research,lactate has shifted from merely a metabolic byproduct to a key regulatory factor in tumor progression.This review aims to clarify how lactate influences tumor development through a dual mechanism of metabolic reprogramming and immune microenvironment regulation.Tumor cells produce large amounts of lactate via the Warburg effect,which not only serves as an energy substrate to support tumor growth but also actively modulates metabolic pathways.The acidic microenvironment formed by lactate accumulation can remodel the extracellular matrix.In the tumor immune microenvironment,acidity suppresses T cell activity;lactylation modifications affect gene expression,favoring tumor immune evasion; and by activating receptor-mediated signaling,they influence immune cell function.These two mechanisms synergistically promote angiogenesis and tumor invasion and metastasis.Based on this,strategies targeting LDHA,lactylation modifications,and related receptors offer hope for tumor therapy.The lactate action framework constructed in this review provides new insights for tumor metabolic immunotherapy.

关键词

乳酸 / 肿瘤微环境 / 免疫逃逸 / 肿瘤转移 / 治疗靶点

Key words

Lactic acid / Tumor microenvironment / Immune escape / Tumor metastasis / Therapeutic target

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基金资助

济宁市重点研发计划项目(2021YXNS033)