Decking, Sonja-Maria and Bruss, Christina and Babl, Nathalie and Bittner, Sebastian and Klobuch, Sebastian and Thomas, Simone and Feuerer, Markus and Hoffmann, Petra and Dettmer, Katja and Oefner, Peter J. and Renner, Kathrin and Kreutz, Marina (2022) LDHB Overexpression Can Partially Overcome T Cell Inhibition by Lactic Acid. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 23 (11): 5970. ISSN , 1422-0067
Full text not available from this repository. (Request a copy)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. Overexpression of the lactate-metabolizing isoenzyme LDHB increased cell respiration and mitigated lactic acid effects on intracellular cytokine production. Strikingly, LDHB-overexpressing cells preferentially migrated 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HIGH LACTATE LEVELS; GLYCOLYSIS; GLUCOSE; DIFFERENTIATION; ACIDIFICATION; ENDOCYTOSIS; METABOLISM; METASTASES; SURVIVAL; PREDICT; T cells; lactic acid; glycolysis; LDH; interferon gamma; adoptive cell transfer; lactate; T cell metabolism |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Frauenheilkunde und Geburtshilfe (Schwerpunkt Frauenheilkunde) Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner) Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Nov 2023 05:53 |
| Last Modified: | 27 Nov 2023 05:53 |
| URI: | https://pred.uni-regensburg.de/id/eprint/56781 |
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