Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I.

ABSTRACT: Immune evasion is a major obstacle for cancer treatment. Common mechanisms of evasion include impaired antigen presentation caused by mutations or loss of heterozygosity of the major histocompatibility complex class I (MHC-I), which has been implicated in resistance to immune checkpoint blockade (ICB) therapy^1-3. However, in pancreatic ductal adenocarcinoma (PDAC), which is resistant to most therapies including ICB⁴, mutations that cause loss of MHC-I are rarely found⁵ despite the frequent downregulation of MHC-I expression^6-8. Here we show that, in PDAC, MHC-I molecules are selectively targeted for lysosomal degradation by an autophagy-dependent mechanism that involves the autophagy cargo receptor NBR1. PDAC cells display reduced expression of M

SUBMITTER: Yamamoto K 

PROVIDER: S-EPMC7296553 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature