Calreticulin mutant myeloproliferative neoplasms induce MHC-I skewing, which can be overcome by an optimized peptide cancer vaccine.

ABSTRACT: The majority of JAK2^V617F-negative myeloproliferative neoplasms (MPNs) have disease-initiating frameshift mutations in calreticulin (CALR), resulting in a common carboxyl-terminal mutant fragment (CALR^MUT), representing an attractive source of neoantigens for cancer vaccines. However, studies have shown that CALR^MUT-specific T cells are rare in patients with CALR^MUT MPN for unknown reasons. We examined class I major histocompatibility complex (MHC-I) allele frequencies in patients with CALR^MUT MPN from two independent cohorts. We observed that MHC-I alleles that present CALR^MUT neoepitopes with high affinity are underrepresented in patients with CALR^MUT MPN. We speculated that this was due to an increased c

SUBMITTER: Gigoux M 

PROVIDER: S-EPMC11182673 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature