Dataset Information

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

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.

SUBMITTER: Brcic L

PROVIDER: S-EPMC8107750 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Brcic Luka L Klikovits Thomas T Megyesfalvi Zsolt Z Mosleh Berta B Sinn Katharina K Hritcu Richard R Laszlo Viktoria V Cufer Tanja T Rozman Ales A Kern Izidor I Mohorcic Katja K Jakopovic Marko M Samarzija Miroslav M Seiwerth Sven S Kolek Vitezslav V Fischer Ondřej O Jakubec Petr P Škarda Jozef J Gieszer Balazs B Hegedus Balazs B Fillinger Janos J Renyi-Vamos Ferenc F Buder Anna A Bilecz Agnes A Berger Walter W Grusch Michael M Hoetzenecker Konrad K Klepetko Walter W Hoda Mir Alireza MA Filipits Martin M Dome Balazs B

Translational lung cancer research 20210401 4

<h4>Background</h4>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).<h4>Methods</h4>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 ...[more]

PMID: 34012777

Similar Datasets

Project description:Malignant pleural mesothelioma (MPM) is a highly lethal, poorly understood neoplasm that is typically associated with asbestos exposure. We performed transcriptional profiling using high-density oligonucleotide microarrays containing approximately 22,000 genes to elucidate potential molecular and pathobiological pathways in MPM using discarded human MPM tumor specimens (n=40), normal lung specimens (n=4), normal pleura specimens (n=5), and MPM and SV40-immortalized mesothelial cell lines (n=5). In global expression analysis using unsupervised clustering techniques, we found two potential subclasses of mesothelioma which correlate loosely with tumor histology. We also identified sets of genes with expression levels that distinguish between multiple tumor subclasses, normal and tumor tissues, and tumors with different morphologies. Microarray gene expression data were confirmed using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and protein analysis for three novel candidate oncogenes (NME2, CRI1, and PDGFC) and one candidate tumor suppressor (GSN). Finally, we used bioinformatics tools (i.e. software) to create and explore complex physiological pathways that may be relevant in mesothelioma tumorigenesis, pathobiology, or both. Tissues and cell lines profiled using microarrays. Discarded MPM surgical specimens (n=40), normal pleura specimens (n=5), and normal lung specimens (n=4) were freshly collected (and snap frozen) from patients who underwent surgery at Boston's Brigham and Women's Hospital (BWH) between October 1998 and August 2000. All of these patients underwent extrapleural pneumonectomy with heated intra-pleural cisplatin chemotherapy delivered after the specimens were removed. All normal specimens were obtained from patients who were never diagnosed with MPM. Two human MPM cell lines (MS589 and MS428) were kindly provided by Jonathan A. Fletcher, M.D., Department of Pathology, BWH. The JMN1B MPM cell line19,20 has been described previously. The SV40-immortalized, non-tumorigenic mesothelial cell line (Met-5A)21 and the MPM cell line MSTO-211H22 were purchased from the American Type Culture Collection. Normal tissues were obtained from additional consented patients undergoing treatment for diseases other than MPM. All MPM samples used in these studies contained relatively pure tumor (greater than 50% tumor cells per high power field examined in a section adjacent to the tissue used). The microscopic slides from the patients' resection specimens were reviewed by one of the authors (J.G.), and the diagnosis and histologic subclassification of MPM confirmed in all cases. Linked clinical and pathological data were obtained for all patients who contributed tumor specimens. Specimens and data were rendered anonymous to protect patient confidentiality. Studies utilizing human tissues were approved by and conducted in accordance with the policies of the Institutional Review Board at BWH.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets