EB病毒相关鼻咽癌PD-L1表达与预后相关性研究

Correlation between PD-L1 Expression and Prognosis in Epstein-Barr Virus-Associated Nasopharyngeal Carcinoma

[目的]探讨鼻咽癌中EB病毒及细胞程序性死亡配体-1(programmed cell death ligand 1,PD-L1)表达及对预后的预测价值。[方法]87例接受根治性放化疗的初治非转移性鼻咽癌患者的病理切片,分别采用原位杂交法(in situ hybridization,ISH)和免疫组化法(immunohistochemistry,IHC)行EB病毒编码小RNA(EBV-encoded RNAs,EBER)和PD-L1表达的检测,并将EB病毒状态和PD-L1表达水平与患者近期疗效及长期预后行相关性分析,主要研究终点包括缓解率(response rates,RR)和总生存率(overall survival,OS)。[结果]87例鼻咽癌原发病灶病理组织切片中,8例(9.2%)EBER表达阴性,79例(90.8%)阳性;1例(1.1%)PD-L1表达阴性,50例(57.5%)低表达,36例(41.4%)高表达。EBER阳性患者中,PD-L1高表达者较多,但差异无统计学意义(P=0.062)。PD-L1高表达与患者较好的预后呈正相关。亚组分析显示在EBER阳性组中,PD-L1高表达与阴性/低表达者的5年无复发生存率(91.8%vs 78.5%,P=0.039,HR=0.382,95%CI:0.142~1.027)和5年无进展生存率(82.5%vs 68.0%,P=0.036,HR=0.363,95%CI:0.135~0.974)差异显著,而在EBER阴性组中,PD-L1表达与预后无明显相关性。[结论]PD-L1高表达与EBV相关鼻咽癌的局部复发和疾病进展相关,深入探讨鼻咽癌的免疫微环境将有助于筛选出免疫治疗的潜在获益人群。

[Objective]To explore the prognostic value of programmed cell death ligand 1(PD-L1)expression in Epstein-Barr virus(EBV)-related nasopharyngeal carcinoma(NPC).[Methods]A total of 87 patients with non-metastatic NPC received radical chemoradiotherapy were enrolled.The presence of EBER(EBV-encoded RNAs)in tumor cells was confirmed by in situ hybridization(ISH),and the expression of PD-L1 was detected by immunohistochemistry(IHC).The impact of EBV status and PD-L1 expression on short-term efficiency and long-term survivals were analyzed.The primary endpoints were response rates(RR)and overall survival(OS).[Results]The negative and positive EBER was detected in 8(9.2%)and 79(90.8%)samples,respectively;and negative,low and high expression of PD-L1 was detected in 1(1.1%),50(57.5%)and 36(41.4%)samples,respectively.EBER positive patients had a trend of high expression of PD-L1,but it was not significant(P=0.062).In EBV positive group,patients with high PD-L1 expression had higher 5-year RFS rate(91.8%vs 78.5%,HR=0.382,95%CI:0.142~1.027,P=0.039)and 5-year PFS rate(82.5%vs 68.0%,P=0.036,HR=0.363,95%CI:0.135~0.974)compared to those with lower PD-L1 expression.[Conclusion]High expression of PD-L1 is associated with local recurrence and disease progression in EBV associated NPC.Exploring the immune microenvironment of NPC will help to screen out potential benefit of immunotherapy.