Prognostic impact of PD-1 and PD-L1 expression in malignant pleural mesothelioma: an international multicenter study

Brcic, Luka and Klikovits, Thomas and Megyesfalvi, Zsolt and Mosleh, Berta and Sinn, Katharina and Hritcu, Richard and Laszlo, Viktoria and Cufer, Tanja and Rozman, Ales and Kern, Izidor and Mohorcic, Katja and Jakopovic, Marko and Samarzija, Miroslav and Seiwerth, Sven and Kolek, Vitezslav and Fischer, Ondřej and Jakubec, Petr and Škarda, Jozef and Gieszer, Balazs and Hegedus, Balazs and Fillinger, Janos and Renyi-Vamos, Ferenc and Buder, Anna and Bilecz, Agnes and Berger, Walter and Grusch, Michael and Hoetzenecker, Konrad and Klepetko, Walter and Hoda, Mir Alireza and Filipits, Martin and Dome, Balazs (2021) Prognostic impact of PD-1 and PD-L1 expression in malignant pleural mesothelioma: an international multicenter study. Translational Lung Cancer Research, 10 (4). pp. 1594-1607. ISSN 2218-6751

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Abstract

Background: 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.

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