TIM-3 levels correlate with enhanced NK cell cytotoxicity and improved clinical outcome in AML patients

Jana Rakova; Iva Truxova; Peter Holicek; Cyril Salek; Michal Hensler; Lenka Kasikova; Josef Pasulka; Monika Holubova; Marek Kovar; Daniel Lysak; Justin P. Kline; Zdenek Racil; Lorenzo Galluzzi; Radek Spisek; Jitka Fucikova

doi:10.1080/2162402X.2021.1889822

TIM-3 levels correlate with enhanced NK cell cytotoxicity and improved clinical outcome in AML patients

Jana Rakova, Iva Truxova, Peter Holicek, Cyril Salek, Michal Hensler, Lenka Kasikova, Josef Pasulka, Monika Holubova, Marek Kovar, Daniel Lysak, Justin P. Kline, Zdenek Racil, Lorenzo Galluzzi, Radek Spisek, Jitka Fucikova

Research output: Contribution to journal › Article › peer-review

35 Scopus citations

Abstract

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.

Original language	English
Article number	1889822
Pages (from-to)	1889822
Journal	Oncoimmunology
Volume	10
Issue number	1
DOIs	https://doi.org/10.1080/2162402X.2021.1889822
State	Published - 2021
Externally published	Yes

Keywords

CD8-Positive T-Lymphocytes
Hepatitis A Virus Cellular Receptor 2
Humans
Killer Cells, Natural
Leukemia, Myeloid, Acute/drug therapy
T-Lymphocytes, Cytotoxic

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1080/2162402X.2021.1889822

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Rakova, J., Truxova, I., Holicek, P., Salek, C., Hensler, M., Kasikova, L., Pasulka, J., Holubova, M., Kovar, M., Lysak, D., Kline, J. P., Racil, Z., Galluzzi, L., Spisek, R., & Fucikova, J. (2021). TIM-3 levels correlate with enhanced NK cell cytotoxicity and improved clinical outcome in AML patients. Oncoimmunology, 10(1), 1889822. Article 1889822. https://doi.org/10.1080/2162402X.2021.1889822

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title = "TIM-3 levels correlate with enhanced NK cell cytotoxicity and improved clinical outcome in AML patients",

abstract = "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.",

keywords = "CD8-Positive T-Lymphocytes, Hepatitis A Virus Cellular Receptor 2, Humans, Killer Cells, Natural, Leukemia, Myeloid, Acute/drug therapy, T-Lymphocytes, Cytotoxic",

author = "Jana Rakova and Iva Truxova and Peter Holicek and Cyril Salek and Michal Hensler and Lenka Kasikova and Josef Pasulka and Monika Holubova and Marek Kovar and Daniel Lysak and Kline, {Justin P.} and Zdenek Racil and Lorenzo Galluzzi and Radek Spisek and Jitka Fucikova",

note = "{\textcopyright} 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.",

year = "2021",

doi = "10.1080/2162402X.2021.1889822",

language = "English",

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pages = "1889822",

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Rakova, J, Truxova, I, Holicek, P, Salek, C, Hensler, M, Kasikova, L, Pasulka, J, Holubova, M, Kovar, M, Lysak, D, Kline, JP, Racil, Z, Galluzzi, L, Spisek, R & Fucikova, J 2021, 'TIM-3 levels correlate with enhanced NK cell cytotoxicity and improved clinical outcome in AML patients', Oncoimmunology, vol. 10, no. 1, 1889822, pp. 1889822. https://doi.org/10.1080/2162402X.2021.1889822

TY - JOUR

T1 - TIM-3 levels correlate with enhanced NK cell cytotoxicity and improved clinical outcome in AML patients

AU - Rakova, Jana

AU - Truxova, Iva

AU - Holicek, Peter

AU - Salek, Cyril

AU - Hensler, Michal

AU - Kasikova, Lenka

AU - Pasulka, Josef

AU - Holubova, Monika

AU - Kovar, Marek

AU - Lysak, Daniel

AU - Kline, Justin P.

AU - Racil, Zdenek

AU - Galluzzi, Lorenzo

AU - Spisek, Radek

AU - Fucikova, Jitka

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - CD8-Positive T-Lymphocytes

KW - Hepatitis A Virus Cellular Receptor 2

KW - Humans

KW - Killer Cells, Natural

KW - Leukemia, Myeloid, Acute/drug therapy

KW - T-Lymphocytes, Cytotoxic

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U2 - 10.1080/2162402X.2021.1889822

DO - 10.1080/2162402X.2021.1889822

M3 - Article

C2 - 33758676

AN - SCOPUS:85102181179

SN - 2162-4011

VL - 10

SP - 1889822

JO - Oncoimmunology

JF - Oncoimmunology

IS - 1

M1 - 1889822

ER -

TIM-3 levels correlate with enhanced NK cell cytotoxicity and improved clinical outcome in AML patients

Abstract

Keywords

UN SDGs

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