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肿瘤浸润淋巴细胞和 PD-L1 表达作为恶性胸膜间皮瘤患者预后的潜在预测指标。

Tumour infiltrating lymphocytes and PD-L1 expression as potential predictors of outcome in patients with malignant pleural mesothelioma.

机构信息

Department of Medicine, Surgery & Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149, Trieste, Italy.

Department of Medicine, Surgery & Health Sciences, University of Trieste, Piazza Ospitale 1, 34129, Trieste, Italy.

出版信息

Mol Biol Rep. 2019 Jun;46(3):2713-2720. doi: 10.1007/s11033-019-04715-9. Epub 2019 Mar 6.

DOI:10.1007/s11033-019-04715-9
PMID:30840203
Abstract

Malignant pleural mesothelioma (MPM) is a rare and aggressive form of tumour. Some mesotheliomas have been proven to be highly immunogenic. Here, we investigated the correlation between tumour infiltrating lymphocytes (TILs) or programmed cell death ligand 1 (PD-L1) expression with overall survival (OS) in patients with MPM. 62 Paraffin-embedded formalin fixed (PEFF) samples were analysed for TILs and PD-L1 expression. Patients were divided in 4 groups according to a cut-off of the percentage of TILs found per sample as measured by immunohistichemistry: "0" or absent (between 0 and 5%), "1" or low (between 6 and 25%), "2" or moderate (between 26 and 50%) and "3" or high (between 51 and 75%). OS was then correlated with different TILs' expression patterns. Moreover, PD-L1 expression was assessed within the tumour as well as in the adjacent stroma on the same samples. Higher expression of peritumoral TILs (Group 2 + 3) versus Group 0 and 1 correlated with improved OS (p-value = 0.02). On the contrary PD-L1 expression seemed to be inversely correlated with clinical outcomes, even in the absence of statistical significance (HR 1.76; p = 0.083 95% IC 0.92-3.36 in areas within the tumour; HR 1.60; p = 0.176 95%; IC 0.80-3.19 in areas within the stroma). No relationship between TILs and PD-L1 expression was identified. Our research supports the use of TILs and PD-L1 expression as potential outcome predictors in patients with MPM. The use of TILs and PD-L1 as biomarkers for checkpoint inhibitors' efficacy warrants future investigation.

摘要

恶性胸膜间皮瘤(MPM)是一种罕见且侵袭性强的肿瘤。一些间皮瘤已被证明具有高度免疫原性。在这里,我们研究了肿瘤浸润淋巴细胞(TILs)或程序性死亡配体 1(PD-L1)表达与 MPM 患者总生存(OS)之间的相关性。分析了 62 例石蜡包埋福尔马林固定(PEFF)样本的 TILs 和 PD-L1 表达。根据免疫组化测量的每个样本中 TILs 的百分比,将患者分为 4 组:“0”或缺失(0 至 5%)、“1”或低(6 至 25%)、“2”或中(26 至 50%)和“3”或高(51 至 75%)。然后将 OS 与不同 TILs 的表达模式相关联。此外,还在同一样本中评估了肿瘤内和相邻基质中的 PD-L1 表达。与 Group 0 和 1 相比,肿瘤周围 TILs(Group 2+3)的高表达与 OS 改善相关(p 值=0.02)。相反,PD-L1 表达似乎与临床结果呈反比相关,尽管没有统计学意义(肿瘤内区域 HR 1.76;p=0.083 95%CI 0.92-3.36;肿瘤内区域 HR 1.60;p=0.176 95%CI 0.80-3.19)。未发现 TILs 和 PD-L1 表达之间存在关系。我们的研究支持将 TILs 和 PD-L1 表达用作 MPM 患者潜在预后预测因子。TILs 和 PD-L1 作为检查点抑制剂疗效的生物标志物值得进一步研究。

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