PD-L1 在卵巢癌中高度表达，与表达 CD44 和其他干细胞标志物的癌症干细胞群体相关。
PD-L1 is highly expressed in ovarian cancer and associated with cancer stem cells populations expressing CD44 and other stem cell markers.
机构信息
Research Center, Biomedical Research Department, King Fahad Specialist Hospital, Dammam, Saudi Arabia.
Department of Pathology and Lab Medicine, King Fahad Specialist Hospital, Dammam, Saudi Arabia.
出版信息
BMC Cancer. 2023 Jan 5;23(1):13. doi: 10.1186/s12885-022-10404-x.
BACKGROUND
Immune checkpoint inhibitors, including PD-L1 (programmed death ligand-1) inhibitors have well documented anticancer therapeutic effect in most types of cancers but its use in the treatment of ovarian cancer is not yet proven. The aim of our study is to explore the predictive biomarkers in ovarian cancer and its association with the outcomes. We have investigated the role of PD-L1 expressions in the tumor microenvironment cells including immune cells and cancer stem cells in different types of ovarian cancer.
METHODS
A total of 119 surgical archived ovarian cancer samples were collected from the pathology department at King Fahad Specialist Hospital, Dammam, Saudi Arabia that included serous carcinomas, clear cell carcinomas, mucinous carcinomas, endometrioid carcinomas, and granulosa cell tumors. Immunohistochemistry (IHC) staining was performed using (i) PD-L1 antibodies to detect PD-L1 expressions; (ii) CD8 and CD4 to detect Tumor Infiltrating Lymphocytes (TILs); and (iii) CD44, LGR5, and ALDH2 to detect stem cell markers. The clinicopathological data were collected from patients' medical record to investigate the association with PD-L1, TILs, and stem cells expressions.
RESULTS
We report high PD-L1 expressions in 47.8% of ovarian cancer samples. PD-L1 expressions were detected in different types of epithelial ovarian cancer and were not associated with poor prognosis of ovarian cancer. However, determining the expression levels of TILs in the ovarian cancer tissues found that 81% (n = 97) of ovarian cancer samples have TILs that express both of CD8 and CD4 and significantly associated with high PD-L1 expressions. Interestingly, we have found that ovarian cancer tissues with high expressions of PD-L1 were associated with high expressions of stem cells expressing CD44 and LGR5.
CONCLUSIONS
PD-L1 is highly expressed in the serous type of ovarian carcinomas and the overall expression of PD-L1 is not associated with poor survival rate. Furthermore, PD-L1 expressions are strongly associated with TILs and stem cell markers in ovarian cancer. Inhibiting the PD-L1 using immune checkpoint inhibitors might downregulate stem cell population that known to be associated with cancer recurrence.
背景
免疫检查点抑制剂，包括 PD-L1（程序性死亡配体-1）抑制剂，在大多数类型的癌症中具有良好的抗癌治疗效果，但在卵巢癌治疗中的应用尚未得到证实。我们的研究旨在探索卵巢癌中的预测生物标志物及其与结局的关系。我们已经研究了 PD-L1 在肿瘤微环境细胞中的表达，包括不同类型卵巢癌中的免疫细胞和癌症干细胞。
方法
从沙特阿拉伯达曼法赫德国王专科医院的病理科共收集了 119 例卵巢癌手术存档样本，包括浆液性癌、透明细胞癌、黏液性癌、子宫内膜样癌和颗粒细胞瘤。使用（i）PD-L1 抗体进行免疫组织化学（IHC）染色，以检测 PD-L1 表达；（ii）CD8 和 CD4 检测肿瘤浸润淋巴细胞（TILs）；（iii）CD44、LGR5 和 ALDH2 检测干细胞标志物。从患者的病历中收集临床病理数据，以研究 PD-L1、TILs 和干细胞表达与临床病理参数的关系。
结果
我们报告了 47.8%的卵巢癌样本中 PD-L1 表达较高。PD-L1 表达存在于不同类型的上皮性卵巢癌中，与卵巢癌的不良预后无关。然而，在卵巢癌组织中检测 TILs 的表达水平发现，81%（n=97）的卵巢癌样本具有同时表达 CD8 和 CD4 的 TILs，且与 PD-L1 高表达显著相关。有趣的是，我们发现 PD-L1 高表达的卵巢癌组织与表达 CD44 和 LGR5 的高表达的干细胞有关。
结论
PD-L1 在浆液性卵巢癌中高度表达，PD-L1 的总体表达与生存率降低无关。此外，PD-L1 表达与卵巢癌中的 TILs 和干细胞标志物密切相关。使用免疫检查点抑制剂抑制 PD-L1 可能会下调与癌症复发相关的干细胞群体。
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