Typing of killer-cell immunoglobulin-like receptors and their cognate human leukocyte antigen class I ligands predicts survival of Chinese Han patients with metastatic non-small-cell lung cancer

摘要

Non-small-cell lung cancer (NSCLC) may establish an immunosuppressive tumor microenvironment that is conducive to tumor growth. Natural killer (NK) cells play a pivotal role in immunological surveillance. Activation of NK cells partially depends on the interactions between killer-cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I ligands. We herein investigated the association of KIRs and HLA ligands with survival in metastatic NSCLC (mNSCLC) patients treated with chemotherapy in a Chinese Han population. Polymerase chain reaction with sequence-specific primers was used to type 15 KIRs at the DNA and mRNA level and 6 HLA ligands in 70 mNSCLC patients. Survival curves were estimated using the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazard regression model was applied for multivariate survival analysis, with the stepwise selection, to determine independent predictors of survival. It was observed that patients with KIR2DS4del gene expression at the mRNA level or HLA-Bw4T80 exhibited poor overall survival (OS). The multivariate analysis revealed that HLA-Bw4T80 and KIR2DS4del expression were independent predictors of OS. This observation indicated that the KIR/HLA ligand is a promising predictor of survival in mNSCLC and may also provide a strategy for treatment stratification and patient management.