Natural killer cell educating KIR/HLA combinations impact survival in anti-PD-L1 treated cancer patients

Abstract Natural killer (NK) cells are educated through the binding of killer immunoglobulin like receptors (KIR) to human leukocyte antigen (HLA) proteins, but it is unknown whether the presence of these highly diverse KIR/HLA interactions influence responses to immunotherapy in solid tumors. We report herein two observations that shed light on NK cell function and abundance in anti-tumor immune responses. In patients with non-small cell lung cancer treated with anti-PD-L1 therapy, we found that individuals carrying HLA-C1 and HLA-Bw4 alleles and the genes coding for their receptors KIR2DL3 and KIR3DL1 showed improved overall survival (OS). Combined with our second finding that NK cell infiltration was independently associated with improved OS, our findings have important implications for precision medicine approaches and the development of NK cell-based therapies.