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

March 8, 2021
Source: Oncoimmunology. 2021 Mar 8;10(1):1889822. doi: 10.1080/2162402X.2021.1889822.

Authors: 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

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.