Association between pH regulation of the tumor microenvironment and immunological state

Frontiers in Oncology

Oncology

Kiyoshi Yoshimura¹  Masahiro Hosonuma¹ 

[1] Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan;Department of Pharmacology, Showa University School of Medicine, Tokyo, Japan;Pharmacological Research Center, Showa University, Tokyo, Japan;Division of Medical Oncology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan;

关键词: pH;    Warburg effect;    lactate;    immune escape;    tumor microenvironment;   

DOI  :  10.3389/fonc.2023.1175563

 received in 2023-02-27, accepted in 2023-04-19,  发布年份 2023

来源: Frontiers

【 摘 要 】

The tumor microenvironment (TME) is characterized by interactions among various cells, including tumor cells, immune cells, stromal cells, and blood vessels mediated by factors such as cytokines and metabolites. The development of cancer immunotherapy in recent years has facilitated a more comprehensive understanding of the TME. The TME changes with cancer type and host immune status, as well as with therapeutic intervention. However, studies on pH regulation of the TME have been mostly based on lactate, a metabolite of tumor cells. Notably, the Warburg effect results in the increased production of secreted lactate, thereby acidifying the extracellular microenvironment and affecting the surrounding cells. Lactate inhibits the activation and proliferation of CD8+ T cells, M1 macrophages, natural killer (NK) cells, and dendritic cells, contributing to tumor cell immune escape. It is also involved in angiogenesis and tissue remodeling, as well as promotes tumor growth and invasion. In this review, we have discussed the lactate-based pH regulation in tumor cells in the TME and its effects on the other constituent cells.

【 授权许可】

Unknown   
Copyright © 2023 Hosonuma and Yoshimura