Molecular markers of MM cell sensitivity and resistance to Natural Killer cells: implications for anti-MM immunotherapy

Abstract

Despite recent therapeutic advances, including monoclonal antibodies and T-cell-based therapies, multiple myeloma (MM) remains incurable. Natural killer (NK) cells are highly cytotoxic in preclinical MM studies; while infusion of ex vivo expanded/activated NK cells in clinical studies has been feasible and safe, without graft-versus-host reactions. However, the molecular markers determining MM cell response vs. resistance to NK cells remain incompletely understood. To address this topic, we performed genome-wide CRISPR/Cas9 loss- (LOF) and gain-of-function (GOF) studies in MM.1S cells exposed to primary NK (pNK) cells and identified genes whose knock-out (KO) or activation led to NK cells resistance or sensitivity.