Oncogenic JAK2^V617F causes PD-L1 expression, mediating immune escape in myeloproliferative neoplasms.

ABSTRACT: Recent evidence has revealed that oncogenic mutations may confer immune escape. A better understanding of how an oncogenic mutation affects immunosuppressive programmed death ligand 1 (PD-L1) expression may help in developing new therapeutic strategies. We show that oncogenic JAK2 (Janus kinase 2) activity caused STAT3 (signal transducer and activator of transcription 3) and STAT5 phosphorylation, which enhanced PD-L1 promoter activity and PD-L1 protein expression in JAK2^V617F-mutant cells, whereas blockade of JAK2 reduced PD-L1 expression in myeloid JAK2^V617F-mutant cells. PD-L1 expression was higher on primary cells isolated from patients with JAK2^V617F-myeloproliferative neoplasms (MPNs) compared to healthy individuals and declined upon JAK2 inhibition.

SUBMITTER: Prestipino A 

PROVIDER: S-EPMC6034655 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature