Hui Yu1, Cory Batenchuk2, Andrzej Badzio3, Theresa A Boyle4, Piotr Czapiewski5, Daniel C Chan1, Xian Lu6, Dexiang Gao6, Kim Ellison1, Ashley A Kowalewski1, Christopher J Rivard1, Rafal Dziadziuszko7, Caicun Zhou8, Maen Hussein9, Donald Richards10, Sharon Wilks11, Marc Monte12, William Edenfield13, Jerome Goldschmidt14, Ray Page15, Brian Ulrich16, David Waterhouse17, Sandra Close18, Jacek Jassem7, Kimary Kulig2, Fred R Hirsch19. 1. Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, Colorado. 2. Bristol-Myers Squibb, Princeton, New Jersey. 3. Radiation Oncology Center NU-Med, Elblag, Poland. 4. Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, Colorado; Department of Pathology, Moffitt Cancer Center, Tampa, Florida. 5. Department of Pathomorphology, Medical University of Gdańsk, Gdańsk, Poland. 6. Department of Biostatisitics and Informatics, University of Colorado Anschutz Medical Campus, Aurora, Colorado. 7. Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland. 8. Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Tongji University Institute, Shanghai, People's Republic of China. 9. Florida Cancer Specialists and Research Institute, Ocala, Florida. 10. Texas Oncology, Tyler, Texas. 11. Cancer Care Centers of South Texas, San Antonio, Texas. 12. Clopton Clinic, Jonesboro, Arkansas. 13. Institute for Translational Oncology Research of Greenville Health System, Greenville, South Carolina. 14. Blue Ridge Cancer Care, Blacksburg, Virginia. 15. The Center for Cancer and Blood Disorders, Fort Worth, Texas. 16. Texas Oncology-Wichita Falls, Texoma Cancer Center, Wichita Falls, Texas. 17. Oncology Hematology Care, Cincinnati, Ohio. 18. Biostats Solutions, Frederick, Maryland. 19. Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, Colorado. Electronic address: Fred.Hirsch@ucdenver.edu.
Abstract
INTRODUCTION: Therapeutic antibodies to immune checkpoints show promising results. Programmed death-ligand 1 (PD-L1), an immune checkpoint ligand, blocks the cancer immunity cycle by binding the PD-L1 receptor (programmed death 1). We investigated PD-L1 protein expression and messenger RNA (mRNA) levels in SCLC. METHODS: PD-L1 protein expression and mRNA levels were determined by immunohistochemistry (IHC) with SP142 and Dako 28-8 PD-L1 antibodies and in situ hybridization in primary tumor tissue microarrays in both tumor cells and tumor-infiltrating immune cells (TIICs) obtained from a limited-disease SCLC cohort of 98 patients. An additional cohort of 96 tumor specimens from patients with extensive-disease SCLC was assessed for PD-L1 protein expression in tumor cells with Dako 28-8 antibody only. RESULTS: The overall prevalence of PD-L1 protein expression in tumor cells was 16.5%. In the limited-disease cohort, the prevalences of PD-L1 protein expression in tumor cells with SP142 and Dako 28-8 were 14.7% and 19.4% (tumor proportion score cutoff ≥1%) and PD-L1 mRNA ISH expression was positive in 15.5% of tumor samples. Increased PD-L1 protein/mRNA expression was associated with the presence of more TIICs (p < 0.05). The extensive-disease cohort demonstrated a 14.9% positivity of PD-L1 protein expression in tumor cells with Dako 28-8 antibody. CONCLUSIONS: A subset of SCLCs is characterized by positive PD-L1 and/or mRNA expression in tumor cells. Higher PD-L1 and mRNA expression correlate with more infiltration of TIICs. The prevalence of PD-L1 in SCLC is lower than that published for NSCLC. The predictive role of PD-L1 expression in SCLC treatment remains to be established.
INTRODUCTION: Therapeutic antibodies to immune checkpoints show promising results. Programmed death-ligand 1 (PD-L1), an immune checkpoint ligand, blocks the cancer immunity cycle by binding the PD-L1 receptor (programmed death 1). We investigated PD-L1 protein expression and messenger RNA (mRNA) levels in SCLC. METHODS:PD-L1 protein expression and mRNA levels were determined by immunohistochemistry (IHC) with SP142 and Dako 28-8 PD-L1 antibodies and in situ hybridization in primary tumor tissue microarrays in both tumor cells and tumor-infiltrating immune cells (TIICs) obtained from a limited-disease SCLC cohort of 98 patients. An additional cohort of 96 tumor specimens from patients with extensive-disease SCLC was assessed for PD-L1 protein expression in tumor cells with Dako 28-8 antibody only. RESULTS: The overall prevalence of PD-L1 protein expression in tumor cells was 16.5%. In the limited-disease cohort, the prevalences of PD-L1 protein expression in tumor cells with SP142 and Dako 28-8 were 14.7% and 19.4% (tumor proportion score cutoff ≥1%) and PD-L1 mRNA ISH expression was positive in 15.5% of tumor samples. Increased PD-L1 protein/mRNA expression was associated with the presence of more TIICs (p < 0.05). The extensive-disease cohort demonstrated a 14.9% positivity of PD-L1 protein expression in tumor cells with Dako 28-8 antibody. CONCLUSIONS: A subset of SCLCs is characterized by positive PD-L1 and/or mRNA expression in tumor cells. Higher PD-L1 and mRNA expression correlate with more infiltration of TIICs. The prevalence of PD-L1 in SCLC is lower than that published for NSCLC. The predictive role of PD-L1 expression in SCLC treatment remains to be established.
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