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

Vadakekolathu Narayanan, J. ORCID: 0000-0002-2671-4285, Minden, M.D., Hood, T., Church, S.E., Reeder, S., Altmann, H., Sullivan, A.H., Viboch, E.J., Patel, T., Ibrahimova, N., Warren, S.E., Arruda, A., Liang, Y., Smith, T.H., Foulds, G.A. ORCID: 0000-0002-2053-7580, Bailey, M.D., Gowen-MacDonald, J., Muth, J., Schmitz, M., Pockley, A.G. ORCID: 0000-0001-9593-6431, Cesano, A., Valk, P.J.M., Löwenberg, B., Bornhäuser, M., Tasian, S.K., Rettig, M.P., Davidson-Moncada, J., DiPersio, J.F. and Rutella, S. ORCID: 0000-0003-1970-7375, 2020. Immune landscapes predict chemotherapy resistance and immunotherapy response in acute myeloid leukemia. Science Translational Medicine, 12 (546): eaaz0463. ISSN 1946-6234

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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.

Item Type: Journal article
Publication Title: Science Translational Medicine
Creators: Vadakekolathu Narayanan, J., Minden, M.D., Hood, T., Church, S.E., Reeder, S., Altmann, H., Sullivan, A.H., Viboch, E.J., Patel, T., Ibrahimova, N., Warren, S.E., Arruda, A., Liang, Y., Smith, T.H., Foulds, G.A., Bailey, M.D., Gowen-MacDonald, J., Muth, J., Schmitz, M., Pockley, A.G., Cesano, A., Valk, P.J.M., Löwenberg, B., Bornhäuser, M., Tasian, S.K., Rettig, M.P., Davidson-Moncada, J., DiPersio, J.F. and Rutella, S.
Publisher: American Association for the Advancement of Science
Date: 3 June 2020
Volume: 12
Number: 546
ISSN: 1946-6234
Identifiers:
NumberType
10.1126/scitranslmed.aaz0463DOI
1331058Other
Divisions: Schools > School of Science and Technology
Record created by: Linda Sullivan
Date Added: 08 Jun 2020 08:21
Last Modified: 25 Jun 2020 14:51
URI: http://irep.ntu.ac.uk/id/eprint/39932

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