Acidity promotes the differentiation of immunosuppressive regulatory T cells.

The metabolic milieu is emerging as a major contributing factor in the maintenance of the immunosuppressive microenvironment within tumours. In particular, the presence of lactic acid produced by highly glycolytic cancer cells is known to suppress antitumour immune cell subsets while promoting immunosuppressive cell populations, such as regulatory T cells (Tregs). Unlike conventional T cells, Tregs have a uniquely potent ability to take up lactic acid to fuel both mitochondrial metabolism and gluconeogenesis, 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 tumours 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 tumour microenvironment. This article is protected by copyright. All rights reserved.