NK cell-based cancer immunotherapy has emerged as an anticancer treatment approach and is currently being tested in clinical trials. KIR2DL5, a member of the human killer cell immunoglobulin-like receptor (KIR) family, has recently been identified as a binding partner for poliovirus receptor (PVR). However, the biology and therapeutic potential of the KIR2DL5/PVR pathway remain widely unexplored.