Lactic Acid Promotes Tumor Growth via Inhibition of IFN-γ Expression - ICMS2015 Abstract Submission Form Tumor Microenvironment Conference

Almut Brand ¹ Katrin Singer ¹ Marina Kreutz ^1,2

¹Department of Internal Medicine III, University Hospital Regensburg, Germany
²Regensburg Center for Interventional Immunology, University of Regensburg, Germany

Tumor-derived lactic acid polarizes tumor-associated macrophages but its impact on tumor-infiltrating T cells is unknown. For this purpose we generated B16.SIY murine melanoma cells with low lactate secretion (Ldha^low) by means of Ldha shRNA. Tumor growth of Ldha^lowcells was significantly delayed in immune competent C57BL/6 mice but not in Rag2^-/- mice lacking lymphocytes. Ldha^low tumors exhibited significantly increased numbers of IFN-γ expressing cells and lactic acid inhibited IFN-γ expression in T cells in vitro. The difference in the tumor growth rate was abolished when tumor clones were injected in IFN-γ^-/- mice. Our findings show that lactic acid is a potent modulator of IFN-γ in tumor-infiltrating T cells.