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TIM-3/Gal-9 interaction induces IFNγ-dependent IDO1 expression in acute myeloid leukemia blast cells
- Source :
- Journal of Hematology & Oncology
- Publication Year :
- 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. Electronic supplementary material The online version of this article (doi:10.1186/s13045-015-0134-4) contains supplementary material, which is available to authorized users.
- Subjects :
- medicine.medical_specialty
Cancer Research
Myeloid
Galectins
Blotting, Western
Enzyme-Linked Immunosorbent Assay
NK cells
Biology
Settore MED/04
Interferon-gamma
Immune system
IDO1
AML
Precursor cell
Internal medicine
hemic and lymphatic diseases
medicine
Humans
Indoleamine-Pyrrole 2,3,-Dioxygenase
Interferon gamma
Molecular Biology
Letter to the Editor
Hepatitis A Virus Cellular Receptor 2
Galectin-9
Cells, Cultured
Chromatography, High Pressure Liquid
Hematology
Immune escape
Myeloid leukemia
Membrane Proteins
medicine.disease
Killer Cells, Natural
Leukemia
Leukemia, Myeloid, Acute
medicine.anatomical_structure
Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA
Oncology
Immunology
Tumor Escape
Bone marrow
medicine.drug
Signal Transduction
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Journal of Hematology & Oncology
- Accession number :
- edsair.doi.dedup.....e5c79e651d7e05377c02b010e86047c4