Early TRAIL-engagement elicits potent multimodal targeting of melanoma by CD34⁺ progenitor cell-derived NK cells.

ABSTRACT: Umbilical cord blood (UCB) CD34⁺ progenitor cell-derived natural killer (NK) cells exert efficient cytotoxicity against various melanoma cell lines. Of interest, the relative cytotoxic performance of individual UCB donors was consistent throughout the melanoma panel and correlated with IFNγ, TNF, perforin and granzyme B levels. Importantly, intrinsic perforin and Granzyme B load predicts NK cell cytotoxic capacity. Exploring the mode of action revealed involvement of the activating receptors NKG2D, DNAM-1, NKp30, NKp44, NKp46 and most importantly of TRAIL. Strikingly, combinatorial receptor blocking led to more pronounced inhibition of cytotoxicity (up to 95%) than individual receptor blocking, especially in combination with TRAIL-blocking, suggesting synergistic cytotoxic NK ce

SUBMITTER: van Vliet AA 

PROVIDER: S-EPMC10329179 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature