Department of Obstetrics and Gynecology, Comprehensive Cancer Center (CCC), Medical University of Vienna, Vienna, Austria.
Division of General Surgery, Department of Surgery, Comprehensive Cancer Center (CCC), Medical University of Vienna, Vienna, Austria.
Sci Rep. 2021 Mar 18;11(1):6400. doi: 10.1038/s41598-021-85966-0.
The therapeutic potential of immune checkpoint inhibitors is currently being investigated in epithelial ovarian cancer (EOC), but immunological effects of the programmed cell death protein 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) axis in EOC still remain poorly understood. The aim of this study was thus to compare infiltration rates of PD-1 and PD-L1 expressing tumor infiltrating leucocytes (TILs) in primary ovarian tumor tissue and metastatic intraperitoneal implants and to investigate its impact on overall survival (OS). Tumor specimens (ovarian tumor tissues and intraperitoneal metastases) of 111 patients were used to investigate the PD-1, PD-L1 and CD8 expression rates on TILs and PD-L1 expression rate of tumor cells. The percentages of CD8, PD-1, and PD-L1 expressing subpopulations of TILs differ in primary ovarian tumor tissues and metastatic intraperitoneal implants. High PD-1 among TILs in peritoneal metastases were associated with favorable OS. High PD-L1 expression in TILs was associated with poor OS. Combining both factors in peritoneal metastases revealed an unfavorable prognosis. Primary ovarian tumor tissue and intraperitoneal metastatic tissues in EOC might have different strategies to evade immune control. Those findings are of importance for the process of biomarker assessment to predict patients' response to immunotherapy.
免疫检查点抑制剂在卵巢上皮癌(EOC)中的治疗潜力正在研究中,但 PD-1/PD-L1 轴在 EOC 中的免疫作用仍知之甚少。因此,本研究旨在比较原发性卵巢肿瘤组织和转移性腹膜内种植体中 PD-1 和 PD-L1 表达的肿瘤浸润性白细胞(TIL)的浸润率,并研究其对总生存期(OS)的影响。使用 111 例患者的肿瘤标本(卵巢肿瘤组织和腹膜内转移)来研究 TIL 上的 PD-1、PD-L1 和 CD8 表达率以及肿瘤细胞上的 PD-L1 表达率。TIL 中 CD8、PD-1 和 PD-L1 表达亚群的百分比在原发性卵巢肿瘤组织和转移性腹膜内种植体中有所不同。腹膜转移中 TIL 中的高 PD-1 与良好的 OS 相关。TIL 中的高 PD-L1 表达与较差的 OS 相关。在腹膜转移中同时考虑这两个因素显示出不利的预后。EOC 中的原发性卵巢肿瘤组织和腹膜内转移组织可能有不同的策略来逃避免疫控制。这些发现对于生物标志物评估过程以预测患者对免疫治疗的反应具有重要意义。