BC Children's Hospital Research Institute, BC Children's Hospital Research Institute, Vancouver, Canada.
Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Eur J Immunol. 2023 Jun;53(6):e2350511. doi: 10.1002/eji.202350511. Epub 2023 May 11.
The metabolic milieu is emerging as a major contributing factor in the maintenance of the immunosuppressive microenvironment within tumors. In particular, the presence of lactic acid produced by highly glycolytic cancer cells is known to suppress antitumor immune cell subsets while promoting immunosuppressive cell populations, such as regulatory T cells (Tregs). Unlike conventional T cells, Tregs have a unique, potent ability to take up lactic acid to fuel both mitochondrial metabolism and gluconeogenesis, thus supporting suppressive function and proliferation. In this issue of the European Journal of Immunology [Eur. J. Immunol. 2023.53:2250258], Rao et al. uncover a novel mechanism by which lactic acid can support Treg accumulation within tumors in mice. This study shows that lactic acid, through a pH-dependent mechanism rather than lactate itself, promotes TGFβ-induced differentiation of Tregs from conventional CD4 T cells. These findings build on the already multifaceted role of lactic acid in maintaining an immunosuppressive tumor microenvironment.
代谢微环境正成为维持肿瘤内免疫抑制微环境的主要因素。特别是，高糖酵解癌细胞产生的乳酸会抑制抗肿瘤免疫细胞亚群，同时促进免疫抑制细胞群体，如调节性 T 细胞（Tregs）。与传统 T 细胞不同，Tregs 具有独特而强大的摄取乳酸的能力，以支持线粒体代谢和糖异生，从而支持抑制功能和增殖。在本期《欧洲免疫学杂志》[Eur. J. Immunol. 2023.53:2250258]中，Rao 等人揭示了乳酸在支持小鼠肿瘤内 Treg 积累的一种新机制。这项研究表明，乳酸通过 pH 依赖性机制而不是乳酸本身促进 TGFβ诱导的常规 CD4 T 细胞向 Tregs 的分化。这些发现建立在乳酸在维持免疫抑制肿瘤微环境中的多方面作用的基础上。
