Author/Editor     Brčić, Luka; Klikovits, Thomas; Megyesfalvi, Zsolt; Mosleh, Berta; Sinn, Katharina; Hritcu, Richard; Laszlo, Viktoria; Čufer, Tanja; Rozman, Aleš; Kern, Izidor; Mohorčič, Katja
Title     Prognostic impact of PD-1 and PD-L1 expression in malignant pleural mesothelioma
Type     članek
Vol. and No.     Letnik 10
Publication year     2021
Volume     str. 1-14
ISSN     2226-4477
Language     eng
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.
Descriptors     Mesothelioma
Prognosis
Mezoteliom
Prognoza
Anatomy and histology
Analysis
Anatomija in histologija
Analiza
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
PD-L1