الملخص
ObjectiveTo identify the relationship between tumor tissue interleukins （ILs） and non-small cell lung cancer （NSCLC） patients with poor response to immune checkpoint blockade （ICB） therapy， and to investigate the differential expression of ILs in tumor of NSCLC patients as well as its effect on ICB response and prognosis. MethodsA total of 61 patients diagnosed with NSCLC and treated with ICB were retrospectively collected from the data of a previous study. We obtained transcriptome sequencing data from tumor tissues and survival data of the patients before ICB treatment. Using bioinformatics methods， we screened for ILs that significantly affected the efficacy and prognosis of ICB treatment. We evaluated the efficacy of ICB treatment using progressive-free survival （PFS） and assessed the prognosis using overall survival （OS）. The Kaplan-Meier survival curve and ROC curve were used to analyze the predictive effect and efficacy of ILs on the efficacy and prognosis of ICB in NSCLC patients. ResultsThe results of the univariate Cox regression analysis in our study showed that nine ILs were found to be associated with OS of NSCLC patients treated with ICB at a significance level of P < 0.1. Further multivariate analysis revealed that high expression of IL-11， IL-17D， and IL-36A was significantly associated with poor prognosis in these patients （P < 0.05）. The results from the Kaplan-Meier survival curve analysis revealed a significant negative correlation between the high expression of IL-17D and both PFS and OS in NSCLC patients. Specifically， patients with IL-17D high expression had a median PFS of 3.1 months compared with 6.5 months in low expression patients ［95% confidence interval （CI） （1.178， 3.655）， P = 0.009］. Similarly， the median OS was 9.8 months in the high expression group versus 21.8 months in the low expression group ［95%CI （1.116， 4.392）， P = 0.018］. ROC curve showed that the prediction performance was favorable ［AUCPFS = 0.702，95%CI （0.562， 0.842）， P = 0.027； AUCOS = 0.684， 95%CI （0.550， 0.818）， P = 0.014］. Although IL-11 and IL-36A alone were not significant predictors of PFS and OS in NSCLC patients， the median PFS and OS were notably shortened to 2.2 months （P = 0.003） and 3.0 months （P < 0.001）， respectively， when high expression of IL-11 and IL-36A was combined with high expression of IL-17D. The ROC curve analysis demonstrated an improvement in prediction efficiency for both PFS and OS in NSCLC patients ［AUCPFS = 0.748， 95%CI （0.615， 0.880）， P = 0.007； AUCOS = 0.703， 95%CI （0.573， 0.833）， P = 0.007］. ConclusionThe results suggest that high expression of IL-11， IL-17D， and IL-36A is associated with a higher risk of disease progression which correlates to poor PFS and OS in NSCLC patients.