Targeting hypoxia at the forefront of anticancer immune responses.

Hypoxia influences immune checkpoint receptors and their respective ligands. In support, we recently demonstrated that hypoxia selectively upregulates programmed cell death ligand 1 (PD-L1) on myeloid-derived suppressor cells (MDSCs) via hypoxia inducible factor 1 α (HIF-1α) binding to a hypoxia-response element (HRE) in the PD-L1 proximal promoter. Furthermore, blockade of PD-L1 under hypoxic conditions enhanced MDSC-mediated T-cell activation by attenuating MDSC secretion of IL-6 and IL-10.