| Literature DB >> 32493790 |
Jayakumar Vadakekolathu1, Mark D Minden2, Tressa Hood3, Sarah E Church3, Stephen Reeder1, Heidi Altmann4, Amy H Sullivan3, Elena J Viboch3, Tasleema Patel5, Narmin Ibrahimova2, Sarah E Warren3, Andrea Arruda2, Yan Liang3, Thomas H Smith3, Gemma A Foulds1, Michael D Bailey3, James Gowen-MacDonald3, John Muth6, Marc Schmitz7,8,9, Alessandra Cesano3, A Graham Pockley1,10, Peter J M Valk11, Bob Löwenberg11, Martin Bornhäuser4,8,9, Sarah K Tasian5, Michael P Rettig12, Jan K Davidson-Moncada6, John F DiPersio12, Sergio Rutella13,10.
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.Entities:
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Year: 2020 PMID： 32493790 PMCID： PMC7427158 DOI： 10.1126/scitranslmed.aaz0463
Source DB: PubMed Journal: Sci Transl Med ISSN： 1946-6234 Impact factor: 17.956