Deletion of Lactate Dehydrogenase-A in Myeloid Cells Triggers Antitumor Immunity.

ABSTRACT: Immunometabolism is emerging as a critical determinant of cancer pathophysiology. In this study, we explored the contributions of macrophage-expressed lactate dehydrogenase-A (LDH-A) to tumor formation in a K-Ras murine model of lung carcinoma. Myeloid-specific deletion of LDH-A promoted accumulation of macrophages with a CD86^high and MCP-1^high M1-like phenotype that suppressed tumor growth. This phenotypic effect was accompanied by reduced VEGF expression and angiogenesis, diminished numbers of PD-L1⁺ cancer cells, increased numbers of CD3⁺ T cells, and activation status of CD8⁺ T cells. Furthermore, it was associated with more pronounced antitumor T-cell immunity via induction of IL17 and IFNγ-producing CD8⁺ T (Tc17 and Tc

SUBMITTER: Seth P 

PROVIDER: S-EPMC5505499 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature