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

Scientific paper - Original scientific paper

• Author: Luka Brcic
• Author: Thomas Klikovits
• Author: Zsolt Megyesfalvi
• Author: Berta Mosleh
• Author: Katharina Sinn
• Author: Richard Hritcu
• Author: Viktoria Laszlo
• Author: Tanja Cufer
• Author: Ales Rozman
• Author: Izidor Kern
• Author: Katja Mohorcic
• Author: Marko Jakopović
• Author: Miroslav Samaržija
• Author: Sven Seiwerth
• Author: Vitezslav Kolek
• Author: Ondřej Fischer
• Author: Petr Jakubec
• Author: Jozef Škarda
• Author: Balazs Gieszer
• Author: Balazs Hegedus
• Author: Janos Fillinger
• Author: Ferenc Renyi-Vamos
• Author: Anna Buder
• Author: Agnes Bilecz
• Author: Walter Berger
• Author: Michael Grusch
• Author: Konrad Hoetzenecker
• Author: Walter Klepetko
• Author: Mir Alireza Hoda
• Author: Martin Filipits
• Author: Balazs Dome
• Author's institution: University of Zagreb; School of Medicine; (Department of Pathology)
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Pathology

Abstract (english)

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).
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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.
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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.
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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.

• Keywords (english): Malignant pleural mesothelioma (MPM); prognosis; programmed cell death 1 (PD-1); programmed death ligand 1 (PD-L1)
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Published version
• Journal title: Translational Lung Cancer Research
• Numbering: vol. 10, no. 4, pp. 1594-1607
• p-ISSN: 2218-6751
• e-ISSN: 2226-4477
• DOI: https://doi.org/10.21037/tlcr-20-1114
• URN:NBN: urn:nbn:hr:105:663503
• Publication: 2021-04
• Document URL: https://tlcr.amegroups.com/article/view/50434/html
• Type of resource: Text
• Access conditions: Open access
• Created on: 2022-01-10 10:20:17