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.

journal_name

Sci Transl Med

authors

Vadakekolathu J,Minden MD,Hood T,Church SE,Reeder S,Altmann H,Sullivan AH,Viboch EJ,Patel T,Ibrahimova N,Warren SE,Arruda A,Liang Y,Smith TH,Foulds GA,Bailey MD,Gowen-MacDonald J,Muth J,Schmitz M,Cesano A,Pockley

doi

10.1126/scitranslmed.aaz0463

subject

Has Abstract

pub_date

2020-06-03 00:00:00

issue

546

eissn

1946-6234

issn

1946-6242

pii

12/546/eaaz0463

journal_volume

12

pub_type

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