Prognostic impact of programmed cell death-1 (PD-1) and PD-ligand 1 (PD-L1) expression in cancer cells and tumor-infiltrating lymphocytes in ovarian high grade serous carcinoma
| Autor: | Jan Budczies, Judith Lindner, Stephan Wienert, Catarina Alisa Kunze, Hagen Kulbe, Jalid Sehouli, Carsten Denkert, Manfred Dietel, Ioana Braicu, Silvia Darb-Esfahani, Michael Bockmayr, Korinna Jöhrens |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
PD-L1 Pathology medicine.medical_specialty Time Factors Programmed Cell Death 1 Receptor Kaplan-Meier Estimate B7-H1 Antigen Disease-Free Survival 03 medical and health sciences 0302 clinical medicine Lymphocytes Tumor-Infiltrating Ovarian carcinoma high grade serous carcinoma PD-1 Databases Genetic Carcinoma Biomarkers Tumor Medicine ovarian Humans RNA Messenger Ovarian Neoplasms Tissue microarray biology business.industry Tumor-infiltrating lymphocytes Reverse Transcriptase Polymerase Chain Reaction Middle Aged medicine.disease Immunohistochemistry Gene Expression Regulation Neoplastic Serous fluid 030104 developmental biology Oncology Tissue Array Analysis 030220 oncology & carcinogenesis tumor-infiltrating lymphocytes Cancer cell biology.protein Cancer research Female Neoplasm Grading business Ovarian cancer Neoplasms Cystic Mucinous and Serous Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Silvia Darb-Esfahani 1,2,* , Catarina Alisa Kunze 1,* , Hagen Kulbe 2,3 , Jalid Sehouli 2,3 , Stephan Wienert 1,4 , Judith Lindner 1 , Jan Budczies 1 , Michael Bockmayr 1 , Manfred Dietel 1 , Carsten Denkert 1,2 , Ioana Braicu 2,3 and Korinna Johrens 1 1 Institute of Pathology, Charite Universitatsmedizin Berlin, Berlin, Germany 2 Tumorbank Ovarian Cancer Network, Department of Gynecology, Charite Universitatsmedizin Berlin, Berlin, Germany 3 Department of Gynecology, Charite Universitatsmedizin Berlin, Berlin, Germany 4 VM Scope GmbH, Berlin, Germany * These authors have contributed equally to the work Correspondence to: Silvia Darb-Esfahani, email: // Keywords : high grade serous carcinoma, ovarian, PD-1, PD-L1, tumor-infiltrating lymphocytes Received : June 12, 2015 Accepted : November 15, 2015 Published : November 29, 2015 Abstract Aims: Antibodies targeting the checkpoint molecules programmed cell death 1 (PD-1) and its ligand PD-L1 are emerging cancer therapeutics. We systematically investigated PD-1 and PD-L1 expression patterns in the poor-prognosis tumor entity high-grade serous ovarian carcinoma. Methods: PD-1 and PD-L1 protein expression was determined by immunohistochemistry on tissue microarrays from 215 primary cancers both in cancer cells and in tumor-infiltrating lymphocytes (TILs). mRNA expression was measured by quantitative reverse transcription PCR. An in silico validation of mRNA data was performed in The Cancer Genome Atlas (TCGA) dataset. Results: PD-1 and PD-L1 expression in cancer cells, CD3+, PD-1+, and PD-L1+ TILs densities as well as PD-1 and PD-L1 mRNA levels were positive prognostic factors for progression-free (PFS) and overall survival (OS), with all factors being significant for PFS ( p < 0.035 each), and most being significant for OS. Most factors also had prognostic value that was independent from age, stage, and residual tumor. Moreover, high PD-1+ TILs as well as PD-L1+ TILs densities added prognostic value to CD3+TILs (PD-1+: p = 0.002,; PD-L1+: p = 0.002). The significant positive prognostic impact of PD-1 and PD-L1 mRNA expression could be reproduced in the TCGA gene expression datasets ( p = 0.02 and p < 0.0001, respectively). Conclusions: Despite their reported immune-modulatory function, high PD-1 and PD-L1 levels are indicators of a favorable prognosis in ovarian cancer. Our data indicate that PD-1 and PD-L1 molecules are biologically relevant regulators of the immune response in high-grade serous ovarian carcinoma, which is an argument for the evaluation of immune checkpoint inhibiting drugs in this tumor entity. |
| Databáze: | OpenAIRE |
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