Blockade of Lactate Dehydrogenase-A (LDH-A) Improves Efficacy of Anti-Programmed Cell Death-1 (PD-1) Therapy in Melanoma.

ABSTRACT: Immunotherapy is a curable treatment for certain cancers, but it is still only effective in a small subset of patients. We have recently reported that programmed cell death protein-1 (PD-1) ligand (PD-L1) expression is regulated by lactate present at high levels in the tumor microenvironment (TME). We hypothesized that the efficacy of anti-PD-1 treatment can be improved by blocking the lactate-generating enzyme, lactate dehydrogenase-A (LDH-A). Anti-PD-1 treatment of mice harboring LDH-A deficient B16-F10 melanoma tumors led to an increase in anti-tumor immune responses compared to mice implanted with tumors expressing LDH-A. Specifically, we observed heightened infiltration of natural killer (NK) cells and CD8⁺ cytotoxic T cells in the LDH-A deficient tumors. These infiltrated cytotoxic c

SUBMITTER: Daneshmandi S 

PROVIDER: S-EPMC6521327 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature