Tumor-priming converts NK cells to memory-like NK cells. (3rd June 2017)

• Record Type: Journal Article
• Authors: Pal, Marina; Schwab, Lisa; Yermakova, Anastasiya; Mace, Emily M.; Claus, Rainer; Krahl, Ann-Christin; Woiterski, Jeanette; Hartwig, Udo F.; Orange, Jordan S.; Handgretinger, Rupert; André, Maya C.
• Is Part Of: Oncoimmunology. Volume 6:Number 6(2017)
• Publication Date: 2017-06-03
• Subjects: Acute B cell precursor leukemia -- adoptive cell transfer -- children -- natural killer cells; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2017.1317411
• Languages: English
• ISSNs: 2162-402X

Abstract

ABSTRACT: Fascinating earlier evidence suggests an intrinsic capacity of human natural killer (NK) cells to acquire adaptive immune features in the context of cytomegalovirus (CMV) infection or pro-inflammatory cytokine stimulation. Since the role of memory NK cells in cancer has so far remained elusive and adoptive NK cell transfer in relapsing pediatric acute B cell precursor leukemia (BCP-ALL) patients awaits improvement, we asked the question whether tumor-priming could promote the generation of memory NK cells with enhanced graft-vs.-leukemia (GvL) reactivity. Here, we provide substantial evidence that priming of naive human NK cells with pediatric acute B cell leukemia or acute myeloid leukemia specimens induces a functional conversion to tumor-induced memory-like (TIML)-NK cells displaying a heightened tumor-specific cytotoxicity and enhanced perforin synthesis. Cell cycles analyses reveal that tumor-priming sustainably alters the balance between NK cell activation and apoptosis in favor of survival. In addition, gene expression patterns differ between TIML- and cytokine-induced memory-like (CIML)-NK cells with the magnitude of regulated genes being distinctly higher in TIML-NK cells. As such, the tumor-induced conversion of NK cells triggers the emergence of a so far unacknowledged NK cell differentiation stage that might promote GvL effects in the context of adoptive cell transfer.