Immune landscapes predict chemotherapy resistance and immunotherapy response in acute myeloid leukemia

Jayakumar Vadakekolathu, Mark D. Minden, Tressa Hood, Sarah E. Church, Stephen Reeder, Heidi Altmann, Amy H. Sullivan, Elena J. Viboch, Tasleema Patel, Narmin Ibrahimova, Sarah E. Warren, Andrea Arruda, Yan Liang, Thomas H. Smith, Gemma A. Foulds, Michael D. Bailey, James Gowen-MacDonald, John Muth, Marc Schmitz, Alessandra CesanoA. Graham Pockley, Peter J.M. Valk, Bob Löwenberg, Martin Bornhäuser, Sarah K. Tasian, Michael P. Rettig, Jan K. Davidson-Moncada, John F. DiPersio, Sergio Rutella

Research output: Contribution to journalArticlepeer-review

109 Scopus citations

Abstract

Acute myeloid leukemia (AML) is a molecularly and clinically heterogeneous hematological malignancy. Although immunotherapy may be an attractive modality to exploit in patients with AML, the ability to predict the groups of patients and the types of cancer that will respond to immune targeting remains limited. This study dissected the complexity of the immune architecture of AML at high resolution and assessed its influence on therapeutic response. Using 442 primary bone marrow samples from three independent cohorts of children and adults with AML, we defined immune-infiltrated and immune-depleted disease classes and revealed critical differences in immune gene expression across age groups and molecular disease subtypes. Interferon (IFN)–γ–related mRNA profiles were predictive for both chemotherapy resistance and response of primary refractory/relapsed AML to flotetuzumab immunotherapy. Our compendium of microenvironmental gene and protein profiles provides insights into the immuno-biology of AML and could inform the delivery of personalized immunotherapies to IFN-γ–dominant AML subtypes.

Original languageEnglish
Article numbereaaz0463
JournalScience translational medicine
Volume12
Issue number546
DOIs
StatePublished - Jun 3 2020

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