OncoImmunology (2021-01-01)

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
https://doi.org/10.1080/2162402X.2021.1889822
Journal volume & issue
Vol. 10, no. 1

Abstract

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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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