Accumulating evidence indicates that immune checkpoint inhibitors (ICIs) can restore CD8+ cytotoxic T lymphocyte (CTL) functions in preclinical models of acute myeloid leukemia (AML). However, ICIs targeting programmed cell death 1 (PDCD1, best known as PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA4) have limited clinical efficacy in patients with AML. Natural killer (NK) cells are central players in AML-targeting immune responses. However, little is known on the relationship between co-inhibitory receptors expressed by NK cells and the ability of the latter to control AML. Here, we show that hepatitis A virus cellular receptor 2 (HAVCR2, best known as TIM-3) is highly expressed by NK cells from AML patients, correlating with improved functional licensing and superior effector functions. Altogether, our data indicate that NK cell frequency as well as TIM-3 expression levels constitute prognostically relevant biomarkers of active immunity against AML.

Biomedical Center Faculty of Medicine in Pilsen Charles University Czech Republic

Caryl and Israel Englander Institute for Precision Medicine New York NY USA

Department of Dermatology Yale University School of Medicine New Haven CT USA

Department of Hematology and Oncology University Hospital in Pilsen Czech Republic

Department of Immunology Charles University 2nd Faculty of Medicine and University Hospital Motol Prague Czech Republic

Department of Medicine University of Chicago Chicago IL USA

Department of Radiation Oncology Weill Cornell Medical College New York NY USA

Institute of Clinical and Experimental Hematology 1st Faculty of Medicine Charles University Prague Czech Republic

Institute of Hematology and Blood Transfusion Prague Czech Republic

Laboratory of Tumor Immunology Institute of Microbiology of the Czech Academy of Sciences Prague Czech Republic

Sandra and Edward Meyer Cancer Center New York NY USA

Sotio Prague Czech Republic

Université de Paris Paris France

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$a TIM-3 levels correlate with enhanced NK cell cytotoxicity and improved clinical outcome in AML patients / $c J. Rakova, I. Truxova, P. Holicek, C. Salek, M. Hensler, L. Kasikova, J. Pasulka, M. Holubova, M. Kovar, D. Lysak, JP. Kline, Z. Racil, L. Galluzzi, R. Spisek, J. Fucikova

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$a Accumulating evidence indicates that immune checkpoint inhibitors (ICIs) can restore CD8+ cytotoxic T lymphocyte (CTL) functions in preclinical models of acute myeloid leukemia (AML). However, ICIs targeting programmed cell death 1 (PDCD1, best known as PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA4) have limited clinical efficacy in patients with AML. Natural killer (NK) cells are central players in AML-targeting immune responses. However, little is known on the relationship between co-inhibitory receptors expressed by NK cells and the ability of the latter to control AML. Here, we show that hepatitis A virus cellular receptor 2 (HAVCR2, best known as TIM-3) is highly expressed by NK cells from AML patients, correlating with improved functional licensing and superior effector functions. Altogether, our data indicate that NK cell frequency as well as TIM-3 expression levels constitute prognostically relevant biomarkers of active immunity against AML.

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