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Dissecting the Immune Landscape of Acute Myeloid Leukemia

MacroGenics Inc., Rockville, MD 20850, USA
NanoString Technologies Inc., Seattle, WA 98109, USA
John van Geest Cancer Research Center, School of Science and Technology, Nottingham Trent University, Nottingham NG11 8NS, UK
Author to whom correspondence should be addressed.
Biomedicines 2018, 6(4), 110;
Received: 2 October 2018 / Revised: 19 November 2018 / Accepted: 21 November 2018 / Published: 25 November 2018
(This article belongs to the Special Issue Dissecting the Immunological Landscape of Human Malignancies)
Acute myeloid leukemia (AML) is a molecularly heterogeneous hematological malignancy with variable response to treatment. Recurring cytogenetic abnormalities and molecular lesions identify AML patient subgroups with different survival probabilities; however, 50–70% of AML cases harbor either normal or risk-indeterminate karyotypes. The discovery of better biomarkers of clinical success and failure is therefore necessary to inform tailored therapeutic decisions. Harnessing the immune system against cancer with programmed death-1 (PD-1)-directed immune checkpoint blockade (ICB) and other immunotherapy agents is an effective therapeutic option for several advanced malignancies. However, durable responses have been observed in only a minority of patients, highlighting the need to gain insights into the molecular features that predict response and to also develop more effective and rational combination therapies that address mechanisms of immune evasion and resistance. We will review the state of knowledge of the immune landscape of AML and identify the broad opportunity to further explore this incompletely characterized space. Multiplexed, spatially-resolved immunohistochemistry, flow cytometry/mass cytometry, proteomic and transcriptomic approaches are advancing our understanding of the complexity of AML-immune interactions and are expected to support the design and expedite the delivery of personalized immunotherapy clinical trials. View Full-Text
Keywords: acute myeloid leukemia; tumor immunological microenvironment; immunotherapy; immune checkpoint blockade; bispecific antibodies acute myeloid leukemia; tumor immunological microenvironment; immunotherapy; immune checkpoint blockade; bispecific antibodies
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Davidson-Moncada, J.; Viboch, E.; Church, S.E.; Warren, S.E.; Rutella, S. Dissecting the Immune Landscape of Acute Myeloid Leukemia. Biomedicines 2018, 6, 110.

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