Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas.
Department of Thoracic Surgery, Kyoto University Hospital, Kyoto, Japan.
Ann Thorac Surg. 2021 Nov;112(5):1575-1583. doi: 10.1016/j.athoracsur.2020.10.031. Epub 2020 Nov 27.
The prognostic role of programmed cell death 1 ligand 1 (PD-L1) in malignant pleural mesothelioma (MPM) is incompletely understood. Our objectives were to evaluate the evidence for tumor PD-L1 as a prognostic biomarker in MPM through meta-analysis and to determine whether tumor PD-L1 expression is associated with survival in MPM patients undergoing macroscopic complete resection.
Meta-analysis was performed to determine the association of PD-L1 with overall survival in MPM (n = 1655) from 14 studies containing overall survival and tumor PD-L1 expression. Univariable and multivariable analyses tested the relationship of tumor PD-L1 with overall survival and recurrence-free survival in an institutional cohort of MPM patients treated by macroscopic complete resection (n = 75). To validate the association of PD-L1 with overall survival, we utilized two independent MPM cohorts (n = 284).
Meta-analysis demonstrated that high tumor PD-L1 expression was associated with poor overall survival. Among 75 patients undergoing macroscopic complete resection, 49 tumors (65%) expressed PD-L1 (1% or more), and high PD-L1 (50% or greater) was more commonly expressed on nonepithelial (29%) compared with epithelial tumors (14%). High tumor PD-L1 expression was independently associated with poor overall survival (P < .001, hazard ratio 5.67) and recurrence-free survival (P = .003, hazard ratio 3.28). The association of PD-L1 overexpression with unfavorable survival was more significant in epithelial MPMs than nonepithelial MPMs. These findings were validated in RNA sequencing analyses in two independent cohorts. Exploratory transcriptome analysis revealed that MPM tumors with PD-L1 overexpression displayed coexpression of other immune regulatory molecules, programmed cell death 1 ligand 2 and T-cell immunoglobulin mucin receptor 3.
Tumor PD-L1 expression is a prognostic biomarker in patients undergoing surgical resection for MPM and may be useful in perioperative decision making.
程序性死亡受体 1 配体 1（PD-L1）在恶性胸膜间皮瘤（MPM）中的预后作用尚未完全阐明。我们的目的是通过荟萃分析评估肿瘤 PD-L1 作为 MPM 预后生物标志物的证据，并确定肿瘤 PD-L1 表达是否与接受大体完全切除的 MPM 患者的生存相关。
荟萃分析用于确定 14 项包含总生存和肿瘤 PD-L1 表达的研究中 PD-L1 与 MPM 总生存的相关性（n=1655）。单变量和多变量分析测试了肿瘤 PD-L1 与机构队列中接受大体完全切除治疗的 MPM 患者的总生存和无复发生存率之间的关系（n=75）。为了验证 PD-L1 与总生存的相关性，我们利用了两个独立的 MPM 队列（n=284）。
荟萃分析表明，高肿瘤 PD-L1 表达与较差的总生存相关。在接受大体完全切除的 75 名患者中，49 例肿瘤（65%）表达 PD-L1（1%或以上），并且在非上皮性肿瘤（29%）中比上皮性肿瘤（14%）更常表达高 PD-L1（50%或以上）。高肿瘤 PD-L1 表达与总生存不良（P<0.001，危险比 5.67）和无复发生存不良（P=0.003，危险比 3.28）独立相关。PD-L1 过表达与上皮性 MPM 相比，与非上皮性 MPM 不良生存的相关性更显著。这些发现在两个独立队列的 RNA 测序分析中得到了验证。探索性转录组分析显示，PD-L1 过表达的 MPM 肿瘤显示出其他免疫调节分子程序性死亡受体 1 配体 2 和 T 细胞免疫球蛋白粘蛋白受体 3 的共表达。
肿瘤 PD-L1 表达是接受 MPM 手术切除患者的预后生物标志物，可能有助于围手术期决策。
