Department of Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, 150040, People's Republic of China.
Department of Radiation Oncology, The Affiliated Hospital of Qingdao University, 266000, Shandong, People's Republic of China.
Cancer Immunol Immunother. 2021 Oct;70(10):2893-2909. doi: 10.1007/s00262-021-02898-4. Epub 2021 Mar 10.
This work investigated the clinical prognostic implications and biological function of plasma soluble programmed cell death ligand 1 in breast cancer patients. Plasma sPD-L1 levels of recurrent/metastatic breast cancer patients were determined, and the association of sPD-L1 levels and metastatic progression-free survival and metastatic overall survival was assessed. The PD-L1 expression on breast cancer cells was analyzed by flow cytometry, and the level of sPD-L1 in the supernatant of breast cancer cells was determined by enzyme-linked immunosorbent assay. Furthermore, the effect of sPD-L1 on the proliferation and apoptosis of T lymphocytes was detected by WST-1 assay and flow cytometry. The plasma sPD-L1 levels in 208 patients with recurrent/metastatic breast cancer before receiving first-line rescue therapy were measured. The optimal cutoff value of plasma sPD-L1 for predicting disease progression was 8.774 ng/ml. Univariate and multivariate analyses identified high sPD-L1 level (≥ 8.774 ng/ml) and visceral metastasis were independent factors associated with poor prognosis. Relevance analysis showed that the plasma sPD-L1 level was weaklyassociated with some systemic inflammation markers, including white cell count (WBC), absolute monocytecount, and absolute neutrophil count. Furthermore, we found sPD-L1 could be found in supernatant of culture with breast cancer cell line expressing PD-L1 on the cell surface and inhibit T lymphocyte function, playing a negative regulatory role in cellular immunity. sPD-L1 was a good tumor predictive maker in breast cancer and it may play a potentially important role in immune tolerance.
这项工作研究了血浆可溶性程序性死亡配体 1 (sPD-L1)在乳腺癌患者中的临床预后意义和生物学功能。测定复发性/转移性乳腺癌患者的血浆 sPD-L1 水平,并评估 sPD-L1 水平与转移性无进展生存期和转移性总生存期的相关性。通过流式细胞术分析乳腺癌细胞上的 PD-L1 表达,并通过酶联免疫吸附试验测定乳腺癌细胞上清液中 sPD-L1 的水平。此外,通过 WST-1 测定法和流式细胞术检测 sPD-L1 对 T 淋巴细胞增殖和凋亡的影响。在接受一线解救治疗前,对 208 例复发性/转移性乳腺癌患者的血浆 sPD-L1 水平进行了测量。预测疾病进展的血浆 sPD-L1 的最佳截断值为 8.774ng/ml。单因素和多因素分析确定高 sPD-L1 水平(≥8.774ng/ml)和内脏转移是与不良预后相关的独立因素。相关性分析表明,血浆 sPD-L1 水平与一些全身炎症标志物(包括白细胞计数、绝对单核细胞计数和绝对中性粒细胞计数)呈弱相关。此外,我们发现 sPD-L1 可存在于表达 PD-L1 的乳腺癌细胞系的培养上清液中,并抑制 T 淋巴细胞功能,在细胞免疫中发挥负调节作用。sPD-L1 是乳腺癌的一个良好的肿瘤预测标志物,它可能在免疫耐受中发挥潜在的重要作用。