@article{913ea3511301482c87f5577701c36f7e,
title = "Immune landscapes predict chemotherapy resistance and immunotherapy response in acute myeloid leukemia",
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.",
author = "Jayakumar Vadakekolathu and Minden, {Mark D.} and Tressa Hood and Church, {Sarah E.} and Stephen Reeder and Heidi Altmann and Sullivan, {Amy H.} and Viboch, {Elena J.} and Tasleema Patel and Narmin Ibrahimova and Warren, {Sarah E.} and Andrea Arruda and Yan Liang and Smith, {Thomas H.} and Foulds, {Gemma A.} and Bailey, {Michael D.} and James Gowen-MacDonald and John Muth and Marc Schmitz and Alessandra Cesano and Pockley, {A. Graham} and Valk, {Peter J.M.} and Bob L{\"o}wenberg and Martin Bornh{\"a}user and Tasian, {Sarah K.} and Rettig, {Michael P.} and Davidson-Moncada, {Jan K.} and DiPersio, {John F.} and Sergio Rutella",
note = "Funding Information: This work was supported by grants from the Qatar National Research Fund (NPRP8-2297-3-494 to S. Rutella); the Roger Counter Foundation, United Kingdom (to A.G.P. and S. Rutella); the John and Lucille van Geest Foundation (to A.G.P. and S. Rutella); the James Skillington Challenge for Leukemia (to A.G.P.); the NCI K08 CA184418 and 1 U01 CA232486 and the Andrew McDonough B+ Foundation (to S.K.T.); and R35CA210084 (to J.F.D.). We also acknowledge support from the National Cancer Institute of the National Institutes of Health under Award Number R50CA211466 (M.P.R.) and St Baldrick{\textquoteright}s Foundation—Stand Up To Cancer (SU2C) Pediatric Cancer Dream Team Translational Research Grant (SU2C-AACR-DT-27-17 to S.K.T.). Stand Up To Cancer is a division of the Entertainment Industry Foundation. Research grants are administered by the American Association for Cancer Research, the scientific partner of SU2C. The Study Alliance of Leukemia (www.sal-aml.org) is gratefully acknowledged for providing primary patient material and clinical data. Funding Information: Funding: This work was supported by grants from the Qatar National Research Fund Publisher Copyright: Copyright {\textcopyright} 2020 The Authors, some rights reserved.",
year = "2020",
month = jun,
day = "3",
doi = "10.1126/scitranslmed.aaz0463",
language = "English",
volume = "12",
journal = "Science Translational Medicine",
issn = "1946-6234",
number = "546",
}