ǂan ǂinternational multicenter study
Luka Brčić (Author), Thomas Klikovits (Author), Zsolt Megyesfalvi (Author), Berta Mosleh (Author), Katharina Sinn (Author), Richard Hritcu (Author), Viktoria Laszlo (Author), Tanja Čufer (Author), Aleš Rozman (Author), Izidor Kern (Author), Katja Mohorčič (Author)

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.

Keywords

maligni plevralni mezoteliom;ligand programirane celične smrti 1;programirana celična smrt 1;PD-L1;malignant pleural mesothelioma;programmed death-ligand 1;programmed cell death 1;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Publisher: AME Publishing
UDC: 616-006
COBISS: 56719619 Link will open in a new window
ISSN: 2226-4477
Views: 690
Downloads: 324
Average score: 0 (0 votes)
Metadata: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Other data

Secondary keywords: Mesothelioma;Anatomy and histology;Analysis;Prognosis;Mezoteliom;Anatomija in histologija;Analiza;Prognoza;
Source comment: Nasl. z nasl. zaslona; Soavtorji iz Slovenije: Tanja Cufer, Ales Rozman, Izidor Kern, Katja Mohorcic; Opis vira z dne 22. 3. 2021;
Pages: str. 1594-1607
Volume: ǂVol. ǂ10
Issue: ǂno. ǂ4
Chronology: Apr. 2021
DOI: 10.21037/tlcr-20-1114
ID: 12712890