Efficacy of PD-1 Blockade Is Potentiated by Metformin-Induced Reduction of Tumor Hypoxia.

ABSTRACT: Blockade of the coinhibitory checkpoint molecule PD-1 has emerged as an effective treatment for many cancers, resulting in remarkable responses. However, despite successes in the clinic, most patients do not respond to PD-1 blockade. Metabolic dysregulation is a common phenotype in cancer, but both patients and tumors are metabolically heterogeneous. We hypothesized that the deregulated oxidative energetics of tumor cells present a metabolic barrier to antitumor immunity through the generation of a hypoxic microenvironment and that normalization of tumor hypoxia might improve response to immunotherapy. We show that the murine tumor lines B16 and MC38 differed in their ability to consume oxygen and produce hypoxic environments, which correlated with their sensitivity to checkpoint blockade.

SUBMITTER: Scharping NE 

PROVIDER: S-EPMC5340074 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature