Rao, Disha and Stunnenberg, Johanna A. A. and Lacroix, Ruben and Dimitriadis, Petros and Kaplon, Joanna and Verburg, Fabienne and van van Royen, Paula T. T. and Hoefsmit, Esmee P. and Renner, Kathrin and Blank, Christian U. U. and Peeper, Daniel S. S. (2023) Acidity-mediated induction of FoxP3+ regulatory T cells. EUROPEAN JOURNAL OF IMMUNOLOGY, 53 (6). ISSN 0014-2980, 1521-4141
Full text not available from this repository. (Request a copy)Abstract
Glucose limitation and increased lactic acid levels are consequences of the elevated glycolytic activity of tumor cells, and constitute a metabolic barrier for the function of tumor infiltrating effector immune cells. The immune-suppressive functions of regulatory T cells (Tregs) are unobstructed in lactic-acid rich environments. However, the impact of lactic acid on the induction of Tregs remains unknown. We observed increased TGF beta-mediated induction of Forkhead box P3(+) (FoxP3(+)) cells in the presence of extracellular lactic acid, in a glycolysis-independent, acidity-dependent manner. These CD4(+) FoxP3(+) cells expressed Treg-associated markers, including increased expression of CD39, and were capable of exerting suppressive functions. Corroborating these results in vivo, we observed that neutralizing the tumor pH by systemic administration of sodium bicarbonate (NaBi) decreased Treg abundance. We conclude that acidity augments Treg induction and propose that therapeutic targeting of acidity in the tumor microenvironment (TME) might reduce Treg-mediated immune suppression within tumors.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LACTIC-ACID; TGF-BETA; TUMOR; METABOLISM; EXPRESSION; CANCER; CHECKPOINT; CONVERSION; RESPONSES; STRESS; Lactic acid; Regulatory T cells; Treg metabolism; Tumor microenvironment |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Hals-Nasen-Ohren-Heilkunde Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 Mar 2024 14:14 |
| Last Modified: | 13 Mar 2024 14:15 |
| URI: | https://pred.uni-regensburg.de/id/eprint/59968 |
Actions (login required)
 |
View Item |
