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.