Oncogenic drivers dictate immune control of acute myeloid leukemia

Autor: Rebecca J. Austin, Jasmin Straube, Rohit Halder, Yashaswini Janardhanan, Claudia Bruedigam, Matthew Witkowski, Leanne Cooper, Amy Porter, Matthias Braun, Fernando Souza-Fonseca-Guimaraes, Simone A. Minnie, Emily Cooper, Sebastien Jacquelin, Axia Song, Tobias Bald, Kyohei Nakamura, Geoffrey R. Hill, Iannis Aifantis, Steven W. Lane, Megan J. Bywater
Rok vydání: 2023
Předmět:
Popis: 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 has not been investigated. 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 NrasG12Dalone 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.Statement of SignificanceThe endogenous immune response against acute myeloid leukemia (AML) is determined by leukemia-specific oncogenic driver mutations. Mutant Nras drives immunological selection of AML.
Databáze: OpenAIRE