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

• Published in: Oncoimmunology 2021-01, Vol.10 (1), p.1889822-1889822
• Main Authors: Rakova, Jana, Truxova, Iva, Holicek, Peter, Salek, Cyril, Hensler, Michal, Kasikova, Lenka, Pasulka, Josef, Holubova, Monika, Kovar, Marek, Lysak, Daniel, Kline, Justin P., Racil, Zdenek, Galluzzi, Lorenzo, Spisek, Radek, Fucikova, Jitka
• Format: Article
• Language: English
• Subjects: CD8-Positive T-Lymphocytes; Co-inhibitory receptor; Hepatitis A Virus Cellular Receptor 2; Humans; innate lymphoid cells; Killer Cells, Natural; lag-3; Leukemia, Myeloid, Acute - drug therapy; Original Research; T-Lymphocytes, Cytotoxic; tigit; vista
• ISSN: 2162-402X; 2162-4011; 2162-402X
• DOI: 10.1080/2162402X.2021.1889822

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.