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.

Folgiero, V., Cifaldi, L., Pira, G. L., Goffredo, B. M., Vinti, L., Locatelli, F., TIM-3/Gal-9 interaction induces IFNγ-dependent IDO1 expression in acute myeloid leukemia blast cells, <<JOURNAL OF HEMATOLOGY & ONCOLOGY>>, 2015; 8 (1): 1-5. [doi:10.1186/s13045-015-0134-4] [https://hdl.handle.net/10807/230066]

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

Locatelli, Franco
Ultimo
Writing – Review & Editing
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.
2015
Inglese
Folgiero, V., Cifaldi, L., Pira, G. L., Goffredo, B. M., Vinti, L., Locatelli, F., TIM-3/Gal-9 interaction induces IFNγ-dependent IDO1 expression in acute myeloid leukemia blast cells, <<JOURNAL OF HEMATOLOGY & ONCOLOGY>>, 2015; 8 (1): 1-5. [doi:10.1186/s13045-015-0134-4] [https://hdl.handle.net/10807/230066]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/230066
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