Immunomodulatory Drugs Exert Anti-Leukemia Effects in Acute Myeloid Leukemia by Direct and Immunostimulatory Activities

Frontiers in Immunology
Aude Le RoyDaniel Olive

Abstract

Immunomodulatory drugs (IMiDs) are anticancer drugs with immunomodulatory, anti-angiogenesis, anti-proliferative, and pro-apoptotic properties. IMiDs are currently used for the treatment of multiple myeloma, myelodysplastic syndrome, and B-cell lymphoma; however, little is known about efficacy in acute myeloid leukemia (AML). We proposed in this study to investigate the relevance of IMiDs therapy for AML treatment. We evaluated the effect of IMiDs on primary AML blasts (n = 24), and the impact in natural killer (NK) cell-mediated immunosurveillance of AML. Using primary AML cells and an immunodeficient mouse leukemia xenograft model, we showed that IMiDs induce AML cell death in vitro and impair leukemia progression in vivo. In addition, treatment of AML blasts with IMiDs resulted in enhanced allogeneic NK cell anti-leukemia reactivity. Treatment by pomalidomide of AML blasts enhanced lysis, degranulation, and cytokine production by primary allogeneic NK cells. Furthermore, the treatment with lenalidomide of patients with myeloid malignancies resulted in NK cell phenotypic changes similar to those observed in vitro. IMiDs increased CD56 and decreased NKp30, NKp46, and KIR2D expression on NK cells. Finally, AML blasts treatment ...Continue Reading

References

Apr 26, 1994·Proceedings of the National Academy of Sciences of the United States of America·R J D'AmatoJ Folkman
Nov 8, 2001·Trends in Immunology·M A CooperM A Caligiuri
Sep 27, 2003·Blood·Richard LeBlancNikhil C Munshi
Dec 20, 2003·The EMBO Journal·Lorenzo Moretta, Alessandro Moretta
Jan 11, 2005·British Journal of Haematology·Toshiaki HayashiKenneth C Anderson
Mar 18, 2005·Annual Review of Immunology·Lewis L Lanier
Aug 24, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Francisco J Hernandez-IlizaliturriMyron S Czuczman
Oct 26, 2005·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Faribourz PayvandiDavid I Stirling
Oct 6, 2006·The New England Journal of Medicine·Alan ListUNKNOWN Myelodysplastic Syndrome-003 Study Investigators
Nov 23, 2007·The New England Journal of Medicine·Meletios DimopoulosUNKNOWN Multiple Myeloma (010) Study Investigators
Jul 17, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Lei WuJ Blake Bartlett
May 28, 2009·Proceedings of the National Academy of Sciences of the United States of America·Sheng WeiAlan List
Feb 9, 2010·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Robert GodalJeffrey S Miller
Oct 20, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·William BlumJohn C Byrd
Dec 30, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Christine I ChenSuzanne Trudel
Jan 8, 2011·Science·Eric VivierSophie Ugolini
Mar 9, 2011·Immunology and Cell Biology·Beatriz Sanchez-CorreaRaquel Tarazona
Apr 2, 2011·Journal of Innate Immunity·Yenan T BrycesonStephanie M Wood
Aug 23, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alice AglianoFrancesco Bertolini
Dec 4, 2012·Cancer Chemotherapy and Pharmacology·Matthew HoffmannGondi Kumar
Jan 16, 2013·Expert Opinion on Investigational Drugs·Yiming Chen, Gautam Borthakur

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Citations

Dec 12, 2019·Anti-cancer Agents in Medicinal Chemistry·Muhammad T IslamMohammad S Mubarak
Sep 10, 2020·Cancers·Antonio PiccolomoFrancesco Albano
Dec 9, 2020·Journal of Hematology & Oncology·Jing Xu, Ting Niu
Mar 12, 2021·Annals of Hematology·Magdalena M BruneUNKNOWN Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON) and Swiss Group for Clinical Cancer Research (SAKK)
Aug 11, 2021·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Meike VoglerEvelyn Ullrich
Sep 10, 2021·Immunotherapy·Essam A TawfikNada M Zaidan

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Methods Mentioned

BETA
MDS
xenograft
density
FCS
flow cytometry
density gradient centrifugation
electrophoresis
PCR
Genotyping
FACS

Software Mentioned

DIVA
GraphPad
GraphPad Prism
Sequence Detection System

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