CD96 promotes natural killer (NK) cell adhesion to target cells expressing the poliovirus receptor (PVR or CD155). Furthermore CD96 stimulates cytotoxicity of activated NK cells, and mediates acquisition of PVR from target cells. This means NK cells have due to the receptor CD96 a dual receptor system that recognizes nectins and nectin-like molecules on target cells and mediates NK cells adhesion and triggering of effector functions. As PVR is highly expressed in certain tumors, this receptor system may be critical for NK cell recognition of tumors.