目的:研究卵巢浆液性腺癌肿瘤微环境中CD8~+肿瘤浸润淋巴细胞(TILs)密度及癌细胞程序性死亡配体-1(PD-L1)的表达情况与临床意义。方法:收集2004年7月至2010年12月于上海交通大学医学院附属仁济医院行肿瘤细胞减灭术的116例卵巢浆液性腺癌患者组织标本,免疫组化检测肿瘤组织CD8~+TILs密度及癌细胞PD-L1表达情况;Spearman相关性分析癌细胞PD-L1表达水平与癌巢及间质CD8~+TILs数目的关系;采用乘积极限法进行基于癌巢CD8~+TILs密度及肿瘤细胞PD-L1表达的单因素生存分析。结果:卵巢浆液性腺癌PD-L1高表达的比例为70.69%(82/116)。癌细胞PD-L1表达强度与癌巢内的CD8~+TILs数目呈显著负相关(P=0.024),而与间质内的CD8~+TILs数目无相关性(P=0.117)。癌巢CD8~+TILs高密度组患者的中位生存时间(64月)显著高于低密度组(43月),差异有统计学意义(P〈0.05);乘积极限法的亚组分析显示肿瘤微环境中癌细胞PD-L1低表达癌巢CD8~+TILs高密度组患者的预后较好。结论:卵巢浆液性腺癌肿瘤微环境中癌巢CD8~+TILs密度及癌细胞PD-L1表达水平与患者预后密切相关,重视肿瘤微环境的免疫分型有助于评估患者预后及筛选合适患者实施抗PD-1/PD-L1免疫治疗。
Objective:To study the expression and prognostic significance of CD8 + tumor-infiltrating lymphocytes(TILs) density and PD-L1 expression in tumor microenvironment of ovarian serous adenocarcinoma. Methods:116 tissue samples of epithelial ovarian serous adenocarcinoma were collected from July 2004 to December 2010 in Renji Hospital of Shanghai Jiaotong University. The intraepithelial,stromal CD8+ TILs density and the expression of PD-L1 in ovarian serous adenocarcinoma were detected by immunohistochemistry. Spearman's coefficient rank test was used to evaluate the correlation between PD-L1 expression and the number of intraepithelial CD8 + TILs. Univariate analysis for overall survival(OS) was performed using the Kaplan-Meier product limit method and survival time difference was compared by the log-rank test. Results=The proportion of high PD-L1 expression in ovarian serous adenocarcinoma was 70.69% (82/116). There was a significant inverse correlation between the number of intraepithelial CD8+ TILs and PD-L1 expression in cancer cells ( P = 0. 024), in contrast, no correlation was found between the number of stromal CD8 + TILs and PD-L1 expression in cancer cells ( P = 0. 117). Patients with high intraepithelial CD8 + TILs density had significantly better median duration of OS than those with low intraepithelial CD8 + TILs density(64 vs 43 months) ( P 〈 0.05). The patient with low PD-L1 expression combined with high intraepithelial CD8 + TILs density in tumor microenvironment had the longest survival time by Kaplan-Meier curves of the four sub-groups. Conclusions:The intraepithelial CD8 + TILs density and expression of PD-L1 in cancer cell are closely related with the prognosis of ovarian serous adenocarcinoma patients. Thus,classifying different types of tumor microenvironment based on the presence or absence of intraepithelial CD8 +TILs and PD-L1 expression helps assess the prognosis of ovarian serous adenocarcinoma patients and screen appropriate patien