Abstract: Objective　To investigate the relationship between the expressions of programmed death ligand-1 (PD-L1) and CD8⁺ tumor infiltrating lymphocytes (TILs) in different locations and clinicopathological features and their effects on the prognosis of patients with lymphocyte-predominant breast cancer (LPBC). Methods　Sixty female patients with LPBC at Department of Pathology, Binzhou Medical University Hospital were selected from January 2011 to December 2018, with a median age of 51; the median diameter of the mass was 2.5 cm; the rate of lymph node metastasis was 40.0%; the histological type was invasive ductal carcinoma. The immunohistochemistry of EnVision method was used to detect the expressions of PD-L1 in tumor cells and immune cells and the expressions of CD8 in stromal (s) and intratumoral (i) TILs. Chi-square test or Fisher exact test and Spearman rank correlation test were used for the correlation analysis, and the Kaplan-Meier method was used for survival analysis and Log-Rank test. Results　The positive expression rate of PD-L1 in LPBC was 81.7% (49/60). The expression of PD-L1 in tumor cells was related to histological grade (P=0.041, P<0.05), and the expression of PD-L1 in immune cells to tumor size and Ki-67 (P=0.004 and 0.001). The high density of CD8⁺sTILs was significantly correlated with better disease-free survival (DFS) (P=0.037), and the high density of CD8⁺iTILs with worse DFS (P=0.042, P<0.05); the expressions of CD8⁺sTILs and CD8⁺iTILs were not correlated with overall survival (OS) (P=0.084 and 0.076). There was a positive correlation between the expression of CD8⁺iTILs and the expression of PD-L1 in tumor cells (r_s=0.301, P=0.019). Conclusions　The high expression of CD8⁺iTILs suggests poor prognosis, while the high expression of CD8⁺sTILs predicts better prognosis. The expression of CD8⁺iTILs is positively correlated with the expression of PD-L1 in tumor cells. Therefore, the poor prognosis of patients with a high expression of CD8⁺iTILs may be due to the inhibition of tumor immunity of CD8⁺iTILs by PD-L1 in tumor cells.

Key words: Breast neoplasms, Lymphocyte-predominant breast cancer, Tumor infiltrating lymphocytes, PD-L1, CD8

摘要： 目的　探讨富于淋巴细胞型乳腺癌（lymphocyte-predominant breast cancer，LPBC）中程序性死亡配体-1（programmed death ligand-1，PD-L1）和CD8⁺肿瘤浸润淋巴细胞（tumor-infiltrating lymphocytes，TILs）在肿瘤中不同部位的表达与临床病理学特征的关系及对患者预后的影响。方法　选取滨州医学院附属医院病理科2011年1月至2018年12月有完整临床病理资料的LPBC 60例，患者均为女性，中位年龄51岁，肿块中位直径为2.5 cm，淋巴结转移率40.0%，组织学类型均为浸润性导管癌。应用免疫组化EnVision法检测PD-L1在肿瘤细胞和免疫细胞中的表达以及CD8在间质（stromal，s）和瘤内（intratumoral，i）TILs中的表达，采用卡方检验或Fisher精确检验、Spearman秩相关检验进行相关性分析，采用Kaplan-Meier法进行生存分析并行Log-Rank检验。结果　LPBC中PD-L1阳性表达率为81.7%（49/60），PD-L1在肿瘤细胞中的表达与组织学分级有关（P=0.041），PD-L1在免疫细胞中的表达与肿瘤大小、Ki-67有关（P=0.004、0.001）。CD8⁺sTILs高密度组与更好的无瘤生存期（DFS）显著相关（P=0.037），CD8⁺iTILs高密度组与更差的DFS显著相关（P=0.042），CD8⁺sTILs和CD8⁺iTILs的表达与总生存期（OS）均无显著相关性（P=0.084、0.076）。CD8⁺iTILs表达与肿瘤细胞中PD-L1表达呈正相关（r_s=0.301，P=0.019）。结论　CD8⁺iTILs高表达的患者预后差，而CD8⁺sTILs高表达的患者预后好，CD8⁺iTILs表达与肿瘤细胞中PD-L1表达呈正相关，CD8⁺iTILs高表达患者预后差可能是由于肿瘤细胞PD-L1抑制了CD8⁺iTILs的肿瘤免疫作用。

关键词: 乳腺肿瘤, 富于淋巴细胞型乳腺癌, 肿瘤浸润淋巴细胞, PD-L1, CD8