Format

Send to

Choose Destination
J Hematol Oncol. 2015 Apr 16;8:36. doi: 10.1186/s13045-015-0134-4.

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

Author information

1
Department of Pediatric Hematology and Oncology, IRCCS Bambino Gesù Children's Hospital, Viale di San Paolo 15, 00146, Rome, Italy. valentina.folgiero@opbg.net.
2
Department of Pediatric Hematology and Oncology, IRCCS Bambino Gesù Children's Hospital, Viale di San Paolo 15, 00146, Rome, Italy. loredana.cifaldi@opbg.net.
3
Department of Pediatric Hematology and Oncology, IRCCS Bambino Gesù Children's Hospital, Viale di San Paolo 15, 00146, Rome, Italy. giuseppina.lipira@opbg.net.
4
Department of Laboratory Medicine, IRCCS Bambino Gesù Children's Hospital, Rome, Italy. biancamaria.goffredo@opbg.net.
5
Department of Pediatric Hematology and Oncology, IRCCS Bambino Gesù Children's Hospital, Viale di San Paolo 15, 00146, Rome, Italy. luciana.vinti@opbg.net.
6
Department of Pediatric Hematology and Oncology, IRCCS Bambino Gesù Children's Hospital, Viale di San Paolo 15, 00146, Rome, Italy. franco.locatelli@opbg.net.
7
Department of Pediatric Science, University of Pavia, Pavia, Italy. franco.locatelli@opbg.net.

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.

PMID:
25886742
PMCID:
PMC4404691
DOI:
10.1186/s13045-015-0134-4
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center