Expression And Prognosis Of PD-L1 And CTLA-4 Proteins In Nasopharyngeal Carcinoma

Objective: The expression of PD-1 and CTLA-4 in tumor is a potential predictive biomarker for immunotherapy.This article systematically analyzed the prognostic factors of 234 patients with primary nasopharyngeal carcinoma.The expression and co-expression of PD-L1 and CTLA-4 proteins were analyzed by IHC,and the relationship between the expression level of PD-L1 and CTLA-4 protein and the prognosis of NPC was further explored.This study provides a reference for finding the best immune checkpoint inhibitor treatment population.Methods: The expression levels of PD-L1 and CTLA-4 protein in 234 patients with primary nasopharyngeal carcinoma were detected by immunohistochemistry.The H-score method was used to score,and the median value was taken as the critical point,and the correlation between the critical point and the OS was analyzed by the ROC curve.The critical points of the H-score of PD-L1 and CTLA-4 proteins were 2 and 3,respectively.Result: The median follow-up of 234 patients was 52.8 months.Among these,48(20.5%),74(31.6%),and 112(47.9%)patients had distant metastases,local recurrence,and disease progression,respectively.62(26.5%)patients died during follow-up.The mean LRFFS,DMFS,PFS,and OS of all patients were 47.8 months,48.6 months,45.3 months,and 51.3 months,respectively.The 3-year LRFFS,DMFS,PFS,and OS were 80.8%,82.9%,75.2%,and 88.5%,respectively.PD-L1 and CTLA-4 protein expression was detected in 181(77.4%)and 163(69.7%),respectively.There were 98 cases(41.9%)with high expression of PD-L1/CTLA-4 and 24 cases(10.2%)with low expression of PD-L1/CTLA-4.The results showed that the LRFFS(P=0.005),PFS(P=0.001)and OS(P=0.018)in the CTLA-4 low expression group were significantly higher than high expression group.PFS(P=0.011)and OS(P=0.001)were higher in the PD-L1 high expression group than low expression group.In the PD-L1/CTLA-4 co-expression group,the PD-L1 high expression/CTLA-4 low expression group had the highest PFS(P=0.026)and OS(P=0.018),and the PD-L1 low expression/CTLA-4 high expression group had the lowest OS,and the four groups of 3 years PFS and OS were 79.1%,83.6%,69.2%,70.4%,and 83.3%,93.2%,76.9%,and 90.8%,respectively.Multivariate analysis confirmed the prognostic value of tumor PD-L1 and CTLA-4 protein expression levels,especially for PFS and OS.Conclusion: Both PD-L1 and CTLA-4 proteins are independent prognostic factors for PFS and OS in patients with primary nasopharyngeal carcinoma.PD-L1 and CTLA-4 proteins are expected to be potential biomarkers for the evaluation of immunotherapy for patients with nasopharyngeal carcinoma.PD-L1/CTLA-4 co-expression is also expected to be a joint biomarker,providing a reference for selecting the best population for immunotherapy.