Fas ligand and lytic granule differentially control cytotoxic dynamics of natural killer cell against cancer target.

ABSTRACT: Interaction dynamics between Natural Killer (NK) cells and cancer targets have been the topic of many previous investigations, but the underlying rate-limiting kinetics and heterogeneity remain poorly understood. In this study, using quantitative single cell microscopy assay, we elucidate the differential dynamic control of NK-cancer cell interaction by multiple cytotoxic pathways. We found primary human NK cell, unlike NK cell line, killed adherent cancer target mainly by lytic granule-independent mechanism, in particular through Fas ligand (FasL). And the distinct kinetics of FasL and lytic granule pathway resulted in significant cell-to-cell variability. Killing by FasL occurred slowly, requiring transient, often multiple NK-cancer cell conjugations that gradually activated caspase-8, w

SUBMITTER: Zhu Y 

PROVIDER: S-EPMC5216932 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature