title: TIM-3/Gal-9 interaction induces IFNγ-dependent IDO1 expression in acute myeloid leukemia blast cells.
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.
authors.affiliation: Department of Pediatric Hematology and Oncology, IRCCS Bambino Gesù Children's Hospital, Viale di San Paolo 15, 00146, Rome, Italy. valentina.folgiero@opbg.net.
authors.forename: Valentina
authors.initials: V
authors.lastname: Folgiero
authors.affiliation: Department of Pediatric Hematology and Oncology, IRCCS Bambino Gesù Children's Hospital, Viale di San Paolo 15, 00146, Rome, Italy. loredana.cifaldi@opbg.net.
authors.forename: Loredana
authors.initials: L
authors.lastname: Cifaldi
authors.affiliation: Department of Pediatric Hematology and Oncology, IRCCS Bambino Gesù Children's Hospital, Viale di San Paolo 15, 00146, Rome, Italy. giuseppina.lipira@opbg.net.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Li Pira
authors.affiliation: Department of Laboratory Medicine, IRCCS Bambino Gesù Children's Hospital, Rome, Italy. biancamaria.goffredo@opbg.net.
authors.forename: Bianca Maria
authors.initials: BM
authors.lastname: Goffredo
authors.affiliation: Department of Pediatric Hematology and Oncology, IRCCS Bambino Gesù Children's Hospital, Viale di San Paolo 15, 00146, Rome, Italy. luciana.vinti@opbg.net.
authors.forename: Luciana
authors.initials: L
authors.lastname: Vinti
authors.affiliation: Department of Pediatric Hematology and Oncology, IRCCS Bambino Gesù Children's Hospital, Viale di San Paolo 15, 00146, Rome, Italy. franco.locatelli@opbg.net.|Department of Pediatric Science, University of Pavia, Pavia, Italy. franco.locatelli@opbg.net.
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
mesh_terms: D015153:Blotting, Western; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004797:Enzyme-Linked Immunosorbent Assay; D037161:Galectins / Q000378:metabolism; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000276:immunology* / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D019139:Tumor Escape / Q000276:immunology*
chemical_list: D037161:Galectins; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; C576710:IDO1 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; C105032:LGALS9 protein, human; D008565:Membrane Proteins; D007371:Interferon-gamma