Hypoxia promotes tumor immune evasion by suppressing MHC-I expression and antigen presentation

ABSTRACT: Hypoxia is a common feature of solid tumors that has previously been linked to resistance to radiotherapy and chemotherapy, and more recently to immunotherapy. In particular, hypoxic tumors exclude T cells and inhibit their activity, suggesting that tumor cells acquire a mechanism to evade T-cell recognition and killing. Our analysis of hypoxic tumors indicates that hypoxia downregulates expression of MHC class I and its bound peptides (i.e., the immunopeptidome). Hypoxia decreases MHC-I expression in an oxygen-dependent manner, via activation of autophagy through the PERK arm of the unfolded protein response. Using an immunopeptidomics-based LC-MS approach, we find a significant reduction of presented antigens under hypoxia. Inhibition of autophagy under hypoxia enhances antigen presentat

SUBMITTER: Prof. Amato, J. Giaccia 

PROVIDER: S-SCDT-10_1038-S44318-024-00319-7 | biostudies-other |

REPOSITORIES: biostudies-other