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

Autor:	Brcic L; Diagnostic and Research Institute of Pathology, Medical University of Graz, Graz, Austria., Klikovits T; Department of Thoracic Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria., Megyesfalvi Z; Department of Thoracic Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria.; Department of Thoracic Surgery, National Institute of Oncology-Semmelweis University, Budapest, Hungary.; National Koranyi Institute of Pulmonology, Budapest, Hungary., Mosleh B; Department of Thoracic Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria., Sinn K; Department of Thoracic Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria., Hritcu R; Department of Thoracic Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria., Laszlo V; Department of Thoracic Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria.; National Koranyi Institute of Pulmonology, Budapest, Hungary., Cufer T; University Clinic for Respiratory and Allergic Diseases Golnik, Golnik, Slovenia., Rozman A; University Clinic for Respiratory and Allergic Diseases Golnik, Golnik, Slovenia.; Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia., Kern I; University Clinic for Respiratory and Allergic Diseases Golnik, Golnik, Slovenia., Mohorcic K; University Clinic for Respiratory and Allergic Diseases Golnik, Golnik, Slovenia., Jakopovic M; Department for Respiratory Diseases Jordanovac, University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia., Samarzija M; Department for Respiratory Diseases Jordanovac, University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia., Seiwerth S; Department of Pathology, University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia., Kolek V; Department of Respiratory Diseases and Tuberculosis, University Hospital Olomouc, Olomouc, Czech Republic., Fischer O; Department of Respiratory Diseases and Tuberculosis, University Hospital Olomouc, Olomouc, Czech Republic., Jakubec P; Department of Respiratory Diseases and Tuberculosis, University Hospital Olomouc, Olomouc, Czech Republic., Škarda J; Institute of Clinical and Molecular Pathology, Medical Faculty, Palacky University Olomouc, Olomouc, Czech Republic.; Department of Pathology, University Hospital Ostrava and Faculty of Medicine University of Ostrava, Ostrava, Czech Republic., Gieszer B; Department of Thoracic Surgery, National Institute of Oncology-Semmelweis University, Budapest, Hungary., Hegedus B; Department of Thoracic Surgery, University Duisburg-Essen, Ruhrlandklinik, Essen, Germany., Fillinger J; Department of Thoracic Surgery, National Institute of Oncology-Semmelweis University, Budapest, Hungary.; National Koranyi Institute of Pulmonology, Budapest, Hungary., Renyi-Vamos F; Department of Thoracic Surgery, National Institute of Oncology-Semmelweis University, Budapest, Hungary.; National Koranyi Institute of Pulmonology, Budapest, Hungary., Buder A; Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna, Austria., Bilecz A; 2nd Department of Pathology, Semmelweis University, Budapest, Hungary., Berger W; Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna, Austria., Grusch M; Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna, Austria., Hoetzenecker K; Department of Thoracic Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria., Klepetko W; Department of Thoracic Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria., Hoda MA; Department of Thoracic Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria., Filipits M; Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna, Austria., Dome B; Department of Thoracic Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria.; Department of Thoracic Surgery, National Institute of Oncology-Semmelweis University, Budapest, Hungary.; National Koranyi Institute of Pulmonology, Budapest, Hungary.
Jazyk:	angličtina
Zdroj:	Translational lung cancer research [Transl Lung Cancer Res] 2021 Apr; Vol. 10 (4), pp. 1594-1607.
DOI:	10.21037/tlcr-20-1114
Abstrakt:	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. Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-20-1114). TK was supported by the Medical Scientific Fund of the Mayor of the City of Vienna (#17028). SS was partly supported by Croatian Science Foundation (grant IP-2014-09-4173). BD, BH and VL were supported by the Austrian Science Fund (FWF I2872, BH; FWF I3522, VL; FWF I3977 and I4677, BD). JF acknowledges funding from the Hungarian National Research, Development and Innovation Office (ANN128666). VL is a recipient of the Bolyai Research Scholarship of the Hungarian Academy of Sciences and the UNKP-19-4 New National Excellence Program of the Ministry for Innovation and Technology. ZM was supported by the UNKP-20-3 New National Excellence Program of the Ministry for Innovation and Technology. The other authors have no conflicts of interest to declare. (2021 Translational Lung Cancer Research. All rights reserved.)
Databáze:	MEDLINE
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