LDHB Overexpression Can Partially Overcome T Cell Inhibition by Lactic Acid
Decking SM, Bruss C, Babl N, Bittner S, Klobuch S, Thomas S, Feuerer M, Hoffmann P, Dettmer K, Oefner PJ, Renner K, Kreutz M (2022)
Publication Type: Journal article
Publication year: 2022
Journal
Book Volume: 23
Article Number: 5970
Journal Issue: 11
DOI: 10.3390/ijms23115970
Abstract
Accelerated glycolysis leads to secretion and accumulation of lactate and protons in the tumor environment and determines the efficacy of adoptive T cell and checkpoint inhibition therapy. Here, we analyzed effects of lactic acid on different human CD4 T cell subsets and aimed to increase CD4 T cell resistance towards lactic acid. In all CD4 T cell subsets analyzed, lactic acid inhibited metabolic activity (glycolysis and respiration), cytokine secretion, and cell proliferation. Overexpres-sion of the lactate-metabolizing isoenzyme LDHB increased cell respiration and mitigated lactic acid effects on intracellular cytokine production. Strikingly, LDHB-overexpressing cells preferentially mi-grated into HCT116 tumor spheroids and displayed higher expression of cytotoxic effector molecules. We conclude, that LDHB overexpression might be a promising strategy to increase the efficacy of adoptive T cell transfer therapy.
Involved external institutions
Leibniz-Institut für Immuntherapie (LIT) / Leibniz Institute for Immunotherapy
Germany (DE)
Universitätsklinikum Regensburg
Germany (DE)
Netherlands Cancer Institute (NKI)
Netherlands (NL)
Universität Regensburg
Germany (DE)
Germany (DE)
Universitätsklinikum Regensburg
Germany (DE)
Netherlands Cancer Institute (NKI)
Netherlands (NL)
Universität Regensburg
Germany (DE)
How to cite
APA:
Decking, S.-M., Bruss, C., Babl, N., Bittner, S., Klobuch, S., Thomas, S.,... Kreutz, M. (2022). LDHB Overexpression Can Partially Overcome T Cell Inhibition by Lactic Acid. International Journal of Molecular Sciences, 23(11). https://doi.org/10.3390/ijms23115970
MLA:
Decking, Sonja-Maria, et al. "LDHB Overexpression Can Partially Overcome T Cell Inhibition by Lactic Acid." International Journal of Molecular Sciences 23.11 (2022).
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