Brcic Luka, Klikovits Thomas, Megyesfalvi Zsolt, Mosleh Berta, Sinn Katharina, Hritcu Richard, Laszlo Viktoria, Cufer Tanja, Rozman Ales, Kern Izidor, Mohorcic Katja, Jakopovic Marko, Samarzija Miroslav, Seiwerth Sven, Kolek Vitezslav, Fischer Ondřej, Jakubec Petr, Škarda Jozef, Gieszer Balazs, Hegedus Balazs, Fillinger Janos, Renyi-Vamos Ferenc, Buder Anna, Bilecz Agnes, Berger Walter, Grusch Michael, Hoetzenecker Konrad, Klepetko Walter, Hoda Mir Alireza, Filipits Martin, Dome Balazs
Diagnostic and Research Institute of Pathology, Medical University of Graz, Graz, Austria.
Department of Thoracic Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria.
Transl Lung Cancer Res. 2021 Apr;10(4):1594-1607. doi: 10.21037/tlcr-20-1114.
Programmed cell death 1/programmed death ligand 1 (PD-1/PD-L1) immune-checkpoint blockade is a promising new therapeutic strategy in cancer. However, expression patterns and prognostic significance of PD-L1 and PD-1 are still controversial in human malignant pleural mesothelioma (MPM).
Formalin-fixed paraffin-embedded (FFPE) tumor samples from 203 MPM patients receiving standard treatment without immunotherapy were collected from 5 European centers. PD-L1 and PD-1 expression of tumor cells (TCs) and tumor-infiltrating lymphocytes (TILs) were measured by immunohistochemistry and correlated with clinical parameters and long-term outcome.
High (>10%) PD-L1 TC and PD-1 TILs expressions were found in 18 (8%) and 39 (24%) patients, respectively. PD-L1 was rarely expressed by TILs [≥1%, n=13 (8%); >10%, n=1]. No significant associations were found between the PD-L1 or PD-1 expression of TCs or TILs and clinicopathological parameters such as stage or histological subtype. Notably, patients with high (>10%) TC-specific PD-L1 expression exhibited significantly worse median overall survival (OS) (6.3 15.1 months of those with low TC PD-L1 expression; HR: 2.51, P<0.001). In multivariate cox regression analysis adjusted for clinical parameters, high TC PD-L1 expression (>10%) proved to be an independent negative prognostic factor for OS (HR: 2.486, P=0.005). There was no significant correlation between PD-L1 or PD-1 expression of TILs and OS.
In this multicenter cohort study, we demonstrate that high (>10%) PD-L1 expression of TCs independently predicts worse OS in MPM. Further studies are warranted to investigate the value of PD-L1/PD-1 expression as a marker for treatment response in MPM patients receiving immunotherapy.
程序性细胞死亡蛋白1/程序性死亡配体1（PD-1/PD-L1）免疫检查点阻断是一种很有前景的癌症新治疗策略。然而，在人类恶性胸膜间皮瘤（MPM）中，PD-L1和PD-1的表达模式及预后意义仍存在争议。
从5个欧洲中心收集了203例接受不含免疫治疗的标准治疗的MPM患者的福尔马林固定石蜡包埋（FFPE）肿瘤样本。通过免疫组织化学检测肿瘤细胞（TCs）和肿瘤浸润淋巴细胞（TILs）的PD-L1和PD-1表达，并将其与临床参数和长期预后相关联。
分别在18例（8%）和39例（24%）患者中发现高（>10%）PD-L1 TCs和PD-1 TILs表达。TILs很少表达PD-L1[≥1%，n = 13（8%）；>10%，n = 1]。未发现TCs或TILs的PD-L1或PD-1表达与临床病理参数如分期或组织学亚型之间存在显著关联。值得注意的是，高（>10%）TC特异性PD-L1表达的患者中位总生存期（OS）明显更差（低TC PD-L1表达者为6.3个月对15.1个月；HR：2.51，P<0.001）。在针对临床参数进行调整的多变量cox回归分析中，高TC PD-L1表达（>10%）被证明是OS的独立阴性预后因素（HR：2.486，P = 0.005）。TILs的PD-L1或PD-1表达与OS之间无显著相关性。
在这项多中心队列研究中，我们证明高（>10%）TC PD-L1表达可独立预测MPM患者更差的OS。有必要进一步研究探讨PD-L1/PD-1表达作为接受免疫治疗的MPM患者治疗反应标志物的价值。
