TY - JOUR
T1 - Immune escape and immunotherapy of acute myeloid leukemia
AU - Vago, Luca
AU - Gojo, Ivana
N1 - Funding Information:
The authors thank Cristina Toffalori for help in drafting the manuscript figures and Judith E. Karp for critical reading of the manuscript. LV acknowledges support from the Italian Ministry of Health (RF-2011-02351998, RF-2011-02348034, and TRANSCAN HLALOSS), the Associazione Italiana per la Ricerca sul Cancro (Start-Up Grant 14162 and IG 22197), and the DKMS Mechtild Harf Foundation (DKMS Mechtild Harf Research Grant 2015). IG acknowledges support from the NIH (UM1-CA186691 and P30-CA006973).
Publisher Copyright:
Copyright: © 2020, American Society for Clinical Investigation.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - In spite of the recent approval of new promising targeted therapies, the clinical outcome of patients with acute myeloid leukemia (AML) remains suboptimal, prompting the search for additional and synergistic therapeutic rationales. It is increasingly evident that the bone marrow immune environment of AML patients is profoundly altered, contributing to the severity of the disease but also providing several windows of opportunity to prompt or rewire a proficient antitumor immune surveillance. In this Review, we present current evidence on immune defects in AML, discuss the challenges with selective targeting of AML cells, and summarize the clinical results and immunologic insights from studies that are testing the latest immunotherapy approaches to specifically target AML cells (antibodies, cellular therapies) or more broadly reactivate antileukemia immunity (vaccines, checkpoint blockade). Given the complex interactions between AML cells and the many components of their environment, it is reasonable to surmise that the future of immunotherapy in AML lies in the rational combination of complementary immunotherapeutic strategies with chemotherapeutics or other oncogenic pathway inhibitors. Identifying reliable biomarkers of response to improve patient selection and avoid toxicities will be critical in this process.
AB - In spite of the recent approval of new promising targeted therapies, the clinical outcome of patients with acute myeloid leukemia (AML) remains suboptimal, prompting the search for additional and synergistic therapeutic rationales. It is increasingly evident that the bone marrow immune environment of AML patients is profoundly altered, contributing to the severity of the disease but also providing several windows of opportunity to prompt or rewire a proficient antitumor immune surveillance. In this Review, we present current evidence on immune defects in AML, discuss the challenges with selective targeting of AML cells, and summarize the clinical results and immunologic insights from studies that are testing the latest immunotherapy approaches to specifically target AML cells (antibodies, cellular therapies) or more broadly reactivate antileukemia immunity (vaccines, checkpoint blockade). Given the complex interactions between AML cells and the many components of their environment, it is reasonable to surmise that the future of immunotherapy in AML lies in the rational combination of complementary immunotherapeutic strategies with chemotherapeutics or other oncogenic pathway inhibitors. Identifying reliable biomarkers of response to improve patient selection and avoid toxicities will be critical in this process.
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U2 - 10.1172/JCI129204
DO - 10.1172/JCI129204
M3 - Article
C2 - 32235097
AN - SCOPUS:85082837557
VL - 130
SP - 1552
EP - 1564
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 4
ER -