Oncogenic drivers dictate immune control of acute myeloid leukemia
Rebecca Austin, Jasmin Straube, Rohit Halder, Yashaswini Janardhanan, Claudia Bruedigam, Matthew T. Witkowski, Leanne Cooper, Amy H. Porter, Matthias Braun, Fernando Souza-Fonseca-Guimarães, Simone A. Minnie, Emily Cooper, Sébastien Jacquelin, Axia Song, Tobias Bald, Kyohei Nakamura, Geoffrey R. Hill, Iannis Aifantis, Steven Lane, Megan J. Bywater
Abstract
Abstract Acute myeloid leukemia (AML) is a genetically heterogeneous, aggressive hematological malignancy induced by distinct oncogenic driver mutations. The effect of specific AML oncogenes on immune activation or suppression is unclear. Here, we examine immune responses in genetically distinct models of AML and demonstrate that specific AML oncogenes dictate immunogenicity, the quality of immune response and immune escape through immunoediting. Specifically, expression of Nras G12D alone is sufficient to drive a potent anti-leukemia response through increased MHC Class II expression that can be overcome with increased expression of Myc. These data have important implications for the design and implementation of personalized immunotherapies for patients with AML.