Department of Tumor Immunology, Radboud Institute of Molecular Life Sciences, Radboud University Medical Centre (Radboudumc), Nijmegen, Netherlands.
Department of Obstetrics and Gynecology, Radboud University Medical Centre (Radboudumc), Nijmegen, Netherlands.
Front Immunol. 2019 Jan 11;9:3156. doi: 10.3389/fimmu.2018.03156. eCollection 2018.
Ascites is a prominent feature of ovarian cancer and could serve as liquid biopsy to assess the immune status of patients. Tumor-infiltrating T lymphocytes are correlated with improved survival in ovarian cancer. To investigate whether immune cells in ascites are associated with patient outcome, we analyzed the amount of dendritic cell (DC) and T cell subsets in ascites from ovarian cancer patients diagnosed with high-grade serous cancer (HGSC). Ascites was collected from 62 HGSC patients prior to chemotherapy. Clinicopathological, histological and follow-up data from patients were collected. Ascites-derived immune cells were isolated using density-gradient centrifugation. The presence of myeloid DCs (BDCA-1, BDCA-3, CD16), pDCs (CD123BDCA-2), and T cells (CD4, CD8) was analyzed using flow cytometry. Complete cytoreduction, response to primary treatment and chemosensitivity were associated with improved patient outcome. In contrast, immune cells in ascites did not significantly correlate with patient survival. However, we observed a trend toward improved outcome for patients having low percentages of CD4 T cells. Furthermore, we assessed the expression of co-stimulatory and co-inhibitory molecules on T cells and non-immune cells in 10 ascites samples. PD-1 was expressed by 30% of ascites-derived T cells and PD-L1 by 50% of non-immune cells. However, the percentage of DC and T cell subsets in ascites was not directly correlated to the survival of HGSC patients.
腹水是卵巢癌的一个显著特征,可作为液体活检来评估患者的免疫状态。肿瘤浸润性 T 淋巴细胞与卵巢癌患者的生存改善相关。为了研究腹水免疫细胞是否与患者的预后相关,我们分析了诊断为高级别浆液性癌 (HGSC) 的卵巢癌患者腹水中树突状细胞 (DC) 和 T 细胞亚群的数量。在化疗前,从 62 名 HGSC 患者中收集腹水。收集患者的临床病理、组织学和随访数据。使用密度梯度离心法从腹水分离出免疫细胞。使用流式细胞术分析髓样 DC (BDCA-1、BDCA-3、CD16)、浆细胞样 DC (CD123BDCA-2) 和 T 细胞 (CD4、CD8) 的存在。完全减瘤、对初始治疗的反应和化疗敏感性与患者的预后改善相关。相反,腹水免疫细胞与患者的生存无显著相关性。然而,我们观察到 CD4 T 细胞百分比低的患者预后改善的趋势。此外,我们评估了 10 个腹水样本中 T 细胞和非免疫细胞上共刺激和共抑制分子的表达。PD-1 在 30%的腹水源性 T 细胞上表达,PD-L1 在 50%的非免疫细胞上表达。然而,腹水 DC 和 T 细胞亚群的百分比与 HGSC 患者的生存无直接相关性。