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Open Access 01-12-2015 | Letter to the Editor

TIM-3/Gal-9 interaction induces IFNγ-dependent IDO1 expression in acute myeloid leukemia blast cells

Authors: Valentina Folgiero, Loredana Cifaldi, Giuseppina Li Pira, Bianca Maria Goffredo, Luciana Vinti, Franco Locatelli

Published in: Journal of Hematology & Oncology | Issue 1/2015

Abstract

NK cells expressing TIM-3 show a marked increase in IFNγ production in response to acute myeloid leukemia (AML) blast cells that endogenously express Gal-9. Herein, we demonstrate that NK cell-mediated production of IFNγ, induced by TIM-3/Gal-9 interaction and released in bone marrow microenvironment, is responsible for IDO1 expression in AML blasts. IDO1-expressing AML blasts consequently down-regulate NK cell degranulation activity, by sustaining leukemia immune escape. Furthermore, the blocking of TIM-3/Gal-9 interaction strongly down-regulates IFNγ-dependent IDO1 activity. Thus, the inhibition of TIM-3/Gal-9 immune check point, which affects NK cell-dependent IFNγ production and the consequent IDO1 activation, could usefully integrate current chemotherapeutic approaches.

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Title: TIM-3/Gal-9 interaction induces IFNγ-dependent IDO1 expression in acute myeloid leukemia blast cells
Authors: Valentina Folgiero
Loredana Cifaldi
Giuseppina Li Pira
Bianca Maria Goffredo
Luciana Vinti
Franco Locatelli
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Journal of Hematology & Oncology / Issue 1/2015
Electronic ISSN: 1756-8722
DOI: https://doi.org/10.1186/s13045-015-0134-4

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