探讨间皮瘤患者胸腔积液中可溶性 PD-L1 的特征：对免疫反应和预后的潜在影响。
Characterization of soluble PD-L1 in pleural effusions of mesothelioma patients: potential implications in the immune response and prognosis.
机构信息
Tumor Epigenetics Unit, IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi, 10, 16132, Genoa, Italy.
Clinical Epidemiology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
出版信息
J Cancer Res Clin Oncol. 2021 Feb;147(2):459-468. doi: 10.1007/s00432-020-03457-7. Epub 2020 Nov 20.
PURPOSE
Programmed death-ligand 1 (PD-L1) protein plays a central role in the antitumor immune response, and appears to be a predictor of prognosis and efficacy for PD-L1 and programmed death 1 (PD-1) blockade therapy. The immunoregulatory role and prognostic impact of PD-L1 soluble form (sPD-L1) have been investigated in biological fluids of patients with different tumors. In malignant pleural mesothelioma (MPM), circulating sPD-L1 has been recently reported in patients' sera, but no data are available in pleural effusions (PE). In our study, we evaluated the baseline expression levels of sPD-L1 in PE from 84 MPM patients and correlated them with PD-L1-status in matched tumors and patients' overall survival (OS).
METHODS
sPD-L1 in PE was determined by ELISA and tumor PD-L1 by immunohistochemistry. Association of sPD-L1 with OS was estimated using the Cox regression model.
RESULTS
We observed that sPD-L1 was variably expressed in all the PE and tended to be higher (by 30%) in patients with PD-L1-positive tumors (cut-off ≥ 1% stained cells) as compared to patients with PD-L1-negative tumors (geometric mean ratio = 1.28, P value = 0.288). sPD-L1 levels were significantly higher than those of sPD-1 (P value = 0.001) regardless of the MPM histotypes and they were positively correlated (r = 0.50, P value < 0.001). Moreover, high PE sPD-L1 concentrations were associated with a trend towards increased OS (hazard ratio 0.79, 95% CL 0.62-1.01, P value = 0.062).
CONCLUSIONS
Our study documents the presence of sPD-L1 in PE of MPM patients, and suggests its possible biological and prognostic role in MPM.
目的
程序性死亡配体 1（PD-L1）蛋白在抗肿瘤免疫反应中发挥核心作用，并且似乎是 PD-L1 和程序性死亡 1（PD-1）阻断治疗的预后和疗效的预测因子。PD-L1 可溶性形式（sPD-L1）在不同肿瘤患者的生物体液中的免疫调节作用和预后影响已经得到了研究。在恶性胸膜间皮瘤（MPM）中，最近在患者的血清中报道了循环 sPD-L1，但在胸腔积液（PE）中尚无数据。在我们的研究中，我们评估了 84 名 MPM 患者的 PE 中 sPD-L1 的基线表达水平，并将其与匹配肿瘤和患者的总体生存（OS）相关联。
方法
通过 ELISA 测定 PE 中的 sPD-L1，通过免疫组织化学测定肿瘤 PD-L1。使用 Cox 回归模型估计 sPD-L1 与 OS 的相关性。
结果
我们观察到 sPD-L1 在所有 PE 中均有不同程度的表达，并且在 PD-L1 阳性肿瘤（截止值≥1％染色细胞）的患者中倾向于更高（高 30％），而在 PD-L1 阴性肿瘤的患者中则更低（几何平均比= 1.28，P 值= 0.288）。sPD-L1 水平明显高于 sPD-1（P 值= 0.001），与 MPM 组织类型无关，并且呈正相关（r = 0.50，P 值<0.001）。此外，PE 中高 sPD-L1 浓度与 OS 增加的趋势相关（危险比 0.79，95％CL 0.62-1.01，P 值= 0.062）。
结论
我们的研究记录了 MPM 患者的 PE 中存在 sPD-L1，并提示其在 MPM 中可能具有生物学和预后作用。
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