| Introduction: With the development of technology in radiotherapy,local-regional control of nasopharyngeal carcinoma(NPC)have a great improvement.But the therapy of relapse and distant metastasis remain a challenge in NPC.Finding a novel biomarker to predict the risk of relapse and distant metastasis is necessary.Programmed death ligand 1(PD-L1)expression represents a mechanism of immune escape by inhibiting T cell immunity.This study aimed to investigate the expression and prognosis of CD8+ TIL and PD-L1 in NPC.Then this study will evaluate the prognosis of immunotype based on CD8+ TIL and PD-L1.Methods and materials: Two hundred and thirty-six patients of NPC without distant metastasis between January 2011 and December 2011 were enrolled.Paraffin-embedded specimens were immunohistochemically stained with PD-L1 and CD8 by Ventana immunohistochemistry autostainer.As distant metastasis is the main treatment failure of NPC,we therefore used the Recursive partitioning analysis(RPA)to find out the best segmentation point according to distant metastasis-free survival.Based on this cut-off value,NPC patients were divided into low CD8+ TIL expression group and high CD8+ TIL expression group.Using Kaplan-Meier method calculate survival rate,then univariate analysis the prognosis using log-rank test according to PD-L1 status and the density of CD8+ TIL.Multivariate analysis study the prognosis of PD-L1 and CD8+ TIL by Cox proportional hazards models.Results: The median follow-up time was 67 months(5-78 months).Forty eight patients died and 43 suffered distant metastasis and 20 developed local or regional relapse during follow-up time.The 5-year overall survival rate(OS)and distant metastasis-free survival rate(DMFS)and local-regional relapse-free survival rate(LRRFS)and progression-free survival rate(PFS)were 78.8%,81.1%,90.5% and 76.4% respectively.In the first part,the study shows that the positive rate of PD-L1 in NPC was 61%.Univariate analysis indicated that PD-L1 positive patients enjoy longer LRRFS than PD-L1 negative patients(94.5% vs.84.4%,p=0.012).Multivariate analysis verified the prognosis of PD-L1(95%CI:0.138-0.868,p=0.024).In the second part,we calculated the cut-off value(1240/mm2)according to RPA,study shows that there are 139 cases in CD8+ TIL high expression group.Univariate analysis indicated that CD8+ TIL high expression group has better prognosis,5-year OS(84.3% vs.70.4%,p=0.024),DMFS(87.8% vs.71.3%,p=0.004),LRRFS(96.8% vs.80.9%,p<0.001)and PFS(85.6% vs.63.1%,p<0.001).Multivariate analysis also support the result.In the third part,the distribution of immunotype showed as following: 90(38.1%)patients with type I(PD-L1+,TILHigh),43(18.2%)patients with type II(PD-L1-,TILLow),54(22.9%)patients with type III(PD-L1+,TILLow)and 49(20.8%)patients with type IV(PD-L1-,TILHigh).Survival analysis indicated that the immunotype was the prognosis of NPC.Data showed that type I NPC patients have better DMFS,LRRFS and PFS,p value is 0.033,<0.001 and 0.002 respectively.Conclusion: This study indicated that PD-L1 status is associated with LRRFS in NPC,and the density of CD8+ TIL is an independent factor of NPC.The immunotype based on PD-L1 and CD8+ TIL are associated with the prognosis of NPC,suggesting that immunotype may be used as a predictor of prognosis of nasopharyngeal carcinoma and guide clinical treatment.In particular,it may be useful for identifying the patients who may benefit from PD-1/PD-L1 inhibitors and guide treatment strategies for immunotherapy. |
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