TitleNatural killer cells induce distinct modes of cancer cell death: Discrimination, quantification, and modulation of apoptosis, necrosis, and mixed forms.
Publication TypeJournal Article
Year of Publication2018
AuthorsBackes, C.S., K. S. Friedmann, S. Mang, A. Knörck, M. Hoth, and C. Kummerow
JournalJ Biol Chem

Immune therapy of cancer is among the promising recent advances in medicine. Whether the immune system can keep cancer in check depends, among other factors, on the efficiency of immune cells to recognize and eliminate cancer cells. We describe a time-resolved single cell assay which reports quality, quantity and kinetics of target cell death induced by single primary human natural killer (NK) cells. The assay reveals that single NK cells induce cancer cell death by apoptosis and necrosis but also by mixed forms. Inhibition of either one of the two major cytotoxic pathways, perforin/granzyme release or FasL/FasR interaction, unmasked the parallel activity of the other one. Ca2+ influx through Orai channels is important for tuning killer cell function. We found that the apoptosis to necrosis ratio of cancer cell death by NK cells is controlled by the magnitude of Ca2+ entry and furthermore by the relative concentrations of perforin and granzyme B. The possibility to change the apoptosis to necrosis ratio employed by NK cells offers an intriguing possibility to modulate the immunogenicity of the tumor microenvironment.














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