乳酸对肿瘤微环境的作用:机制、对免疫细胞的影响及治疗意义

Lactate Contribution to the Tumor Microenvironment: Mechanisms, Effects on Immune Cells and Therapeutic Relevance.

作者信息

Romero-Garcia Susana, Moreno-Altamirano María Maximina B, Prado-Garcia Heriberto, Sánchez-García Francisco Javier

机构信息

Chronic-Degenerative Department, National Institute of Respiratory Diseases "Ismael Cosio Villegas" , Mexico City , Mexico.

Laboratorio de Inmunorregulación, Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional , Mexico City , Mexico.

出版信息

Front Immunol. 2016 Feb 16;7:52. doi: 10.3389/fimmu.2016.00052. eCollection 2016.

Abstract

Malignant transformation of cells leads to enhanced glucose uptake and the conversion of a larger fraction of pyruvate into lactate, even under normoxic conditions; this phenomenon of aerobic glycolysis is largely known as the Warburg effect. This metabolic reprograming serves to generate biosynthetic precursors, thus facilitating the survival of rapidly proliferating malignant cells. Extracellular lactate directs the metabolic reprograming of tumor cells, thereby serving as an additional selective pressure. Besides tumor cells, stromal cells are another source of lactate production in the tumor microenvironment, whose role in both tumor growth and the antitumor immune response is the subject of intense research. In this review, we provide an integral perspective of the relationship between lactate and the overall tumor microenvironment, from lactate structure to metabolic pathways for its synthesis, receptors, signaling pathways, lactate-producing cells, lactate-responding cells, and how all contribute to the tumor outcome. We discuss the role of lactate as an immunosuppressor molecule that contributes to tumor evasion and we explore the possibility of targeting lactate metabolism for cancer treatment, as well as of using lactate as a prognostic biomarker.

摘要

细胞的恶性转化会导致葡萄糖摄取增加,并且即使在常氧条件下,也会有更大比例的丙酮酸转化为乳酸;这种有氧糖酵解现象在很大程度上被称为瓦伯格效应。这种代谢重编程有助于生成生物合成前体,从而促进快速增殖的恶性细胞的存活。细胞外乳酸引导肿瘤细胞的代谢重编程,从而成为一种额外的选择压力。除了肿瘤细胞,基质细胞是肿瘤微环境中乳酸产生的另一个来源,其在肿瘤生长和抗肿瘤免疫反应中的作用是深入研究的主题。在本综述中,我们从乳酸结构到其合成的代谢途径、受体、信号通路、产生乳酸的细胞、对乳酸有反应的细胞,以及所有这些如何影响肿瘤结局等方面,提供了乳酸与整体肿瘤微环境之间关系的完整视角。我们讨论了乳酸作为一种有助于肿瘤逃逸的免疫抑制分子的作用,并探讨了针对乳酸代谢进行癌症治疗的可能性,以及将乳酸用作预后生物标志物的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd0d/4754406/9cab9f09d642/fimmu-07-00052-g001.jpg

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