| First Author | Brand A | Year | 2016 |
| Journal | Cell Metab | Volume | 24 |
| Issue | 5 | Pages | 657-671 |
| PubMed ID | 27641098 | Mgi Jnum | J:251926 |
| Mgi Id | MGI:6107115 | Doi | 10.1016/j.cmet.2016.08.011 |
| Citation | Brand A, et al. (2016) LDHA-Associated Lactic Acid Production Blunts Tumor Immunosurveillance by T and NK Cells. Cell Metab 24(5):657-671 |
| abstractText | 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 IFN-gamma-producing T and NK cells. However, in Rag2(-/-)gammac(-/-) mice, lacking lymphocytes and NK cells, and in Ifng(-/-) mice, Ldha(low) and control cells formed tumors at similar rates. Pathophysiological concentrations of lactic acid prevented upregulation of nuclear factor of activated T cells (NFAT) in T and NK cells, resulting in diminished IFN-gamma production. Database analyses revealed negative correlations between LDHA expression and T cell activation markers in human melanoma patients. Our results demonstrate that lactic acid is a potent inhibitor of function and survival of T and NK cells leading to tumor immune escape. |
