Fischer, Karin and Hoffmann, Petra and Voelkl, Simon and Meidenbauer, Norbert and Ammer, Julia and Edinger, Matthias and Gottfried, Eva and Schwarz, Sabine and Rothe, Gregor and Hoves, Sabine and Renner, Kathrin and Timischl, Birgit and Mackensen, Andreas and Kunz-Schughart, Leoni and Andreesen, Reinhard and Krause, Stefan W. and Kreutz, Marina (2007) Inhibitory effect of tumor cell-derived lactic acid on human T cells. BLOOD, 109 (9). pp. 3812-3819. ISSN 0006-4971,
Full text not available from this repository. (Request a copy)Abstract
A characteristic feature of tumors is high production of lactic acid due to enhanced glycolysis. Here, we show a positive correlation between lactate serum levels and tumor burden in cancer patients and examine the influence of lactic acid on immune functions in vitro. Lactic acid suppressed the proliferation and cytokine production of human cytotoxic T lymphocytes (CTLs) up to 95% and led to a 50% decrease in cytotoxic activity. A 24-hour recovery period in lactic acid-free medium restored CTL function. CTLs infiltrating lactic acid-producing multicellular tumor spheroids showed a reduced cytokine production. Pretreatment of tumor spheroids with an inhibitor of lactic acid production prevented this effect. Activated T cells themselves use glycolysis and rely on the efficient secretion of lactic acid, as its intracellular accumulation disturbs their metabolism. Export by monocarboxylate transporter-1 (MCT-1) depends on a gradient between cytoplasmic and extracellular lactic acid concentrations and consequently, blockade of MCT-1 resulted in impaired CTL function. We conclude that high lactic acid concentrations in the tumor environment block lactic acid export in T cells, thereby disturbing their metabolism and function. These findings suggest that targeting this metabolic pathway in tumors is a promising strategy to enhance tumor. (C) 2007 by The American Society of Hematology.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HIGH LACTATE LEVELS; MELANOMA PATIENTS; CAPILLARY-ELECTROPHORESIS; AEROBIC GLYCOLYSIS; EXTRACELLULAR PH; ACTIVATION; HYPOXIA; EXPRESSION; CANCERS; TARGET; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner) Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 Dec 2020 10:51 |
| Last Modified: | 10 Dec 2020 10:51 |
| URI: | https://pred.uni-regensburg.de/id/eprint/32787 |
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