STAT1 acts as a tumor promoter for leukemia development

SummaryThe tumor suppressor STAT1 is considered a key regulator of the surveillance of developing tumors. Here, we describe an unexpected tumor-promoting role for STAT1 in leukemia. STAT1−/− mice are partially protected from leukemia development, and STAT1−/− tumor cells induce leukemia in RAG2−/− and immunocompetent mice with increased latency. The low MHC class I protein levels of STAT1−/− tumor cells enable efficient NK cell lysis and account for the enhanced tumor clearance. Strikingly, STAT1−/− tumor cells acquire increased MHC class I expression upon leukemia progression. These findings define STAT1 as a tumor promoter in leukemia development. Furthermore, we describe the upregulation of MHC class I expression as a general mechanism that allows for the escape of hematopoietic malignancies from immune surveillance.