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LDHA-Associated Lactic Acid Production Blunts Tumor Immunosurveillance by T and NK Cells

Brand, A. ; Singer, K. ; Koehl, G. E. ; Kolitzus, M. ; Schoenhammer, G. ; Thiel, A. ; Matos, C. ; Bruss, C. ; Klobuch, S. ; Peter, K. ; Kastenberger, M. ; Bogdan, C. ; Schleicher, U. ; Mackensen, Andreas ; Ullrich, E. ; Fichtner-Feigl, S. ; Kesselring, R. ; Mack, M. ; Ritter, U. ; Schmid, M. ; Blank, C. ; Dettmer, Katja ; Oefner, Peter J. ; Hoffmann, P. ; Walenta, S. ; Geissler, E. K. ; Pouyssegur, J. ; Villunger, A. ; Steven, A. ; Seliger, B. ; Schreml, S. ; Haferkamp, S. ; Kohl, E. ; Karrer, S. ; Berneburg, Mark ; Herr, Wolfgang ; Mueller-Klieser, W. ; Renner, K. ; Kreutz, Marina



Abstract

Elevated lactate dehydrogenase A (LDHA) expression is associated with poor outcome in tumor patients. Here we show that LDHA-associated lactic acid accumulation in melanomas inhibits tumor surveillance by T and NK cells. In immunocompetent C57BL/6 mice, tumors with reduced lactic acid production (Ldha(low)) developed significantly slower than control tumors and showed increased infiltration with ...

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