TIM-3 levels correlate with enhanced NK cell cytotoxicity and improved clinical outcome in AML patients
Jana Raková, Iva Truxová, Peter Holíček, Cyril Šálek, Michal Hensler, Lenka Kašíková, Josef Pasulka, Monika Holubová, Marek Kovář, Daniel Lysák, Justin Kline, Zdeněk Ráčil, Lorenzo Galluzzi, Radek Špíšek, Jitka Fučíková
Abstract
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.