Activating KIRs on educated NK cells support downregulation of CD226 and inefficient tumor immunosurveillance

Therapies using NK cells (NKcs) expanded/activated ex vivo or stimulated in vivo with new immunostimulatory agents offer alternative opportunities for patients with recurrent/refractory tumors, but relevant biomarkers to guide the selection of patients are required for optimum results. Overall survival of 249 solid cancer patients was evaluated in relation to the genetics and/or the expression on peripheral blood NKcs of inhibitory and activating killer-cell immunoglobulin-like receptors (iKIRs and aKIRs, respectively), HLA class I ligands, CD226 (also known as DNAM-1), and NKG2A. Compared to patients with higher expression, patients with low expression of CD226 on total NKcs showed shorter mean overall survival (60.7 vs. 98.0 months, P