Prognostic impact of PD-1 and PD-L1 expression in malignant pleural mesothelioma : an international multicenter studyBrčić, Luka (Avtor) Klikovits, Thomas (Avtor) Megyesfalvi, Zsolt (Avtor) Mosleh, Berta (Avtor) Sinn, Katharina (Avtor) Hritcu, Richard (Avtor) Laszlo, Viktoria (Avtor) Čufer, Tanja (Avtor) Rozman, Aleš (Avtor) Kern, Izidor (Avtor) Mohorčič, Katja (Avtor) mesothelioma - anatomy and histology - analysis1malignant pleural mesotheliomaprogrammed death-ligand 1programmed cell death 1PD-L1Background: 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). Methods: 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. Results: 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 vs. 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. Conclusions: 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.AME Publishing20212021-03-31 14:34:03Neznano13805sl© Translational Lung Cancer Research