PD-1 and PD-L1 Expression on Canine Urothelial Carcinoma Cell Lines and the Relative Expression of Lymphocyte PD-1 in Canine Urothelial Carcinoma Patients
2020 VCS Virtual Conference
Christopher Pinard1; Ashley Stegelmeier2; Jordon Inkol3; Andrew Poon3; Anthony Mutsaers4; Geoffrey Wood2; Darren Wood2; J. Paul Woods1; Samuel Hocker5
1Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada; 2Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada; 3Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada; 4Departments of Clinical Studies and Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada; 5Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada and Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA
Introduction
Urothelial carcinoma (UC) is the most common urinary bladder tumor in dogs. Despite combination therapies, most patients succumb to local tumor progression or metastatic disease. The programmed death receptor (PD-1) and its ligand (PD-L1) have been studied in a variety of human cancers. Consequently, therapies directed at PD-1 and/or PD-L1 are now incorporated into the treatment of muscle invasive UC in people. Presently, limited data exists about the expression of PD-1/PD-L1 in dogs, especially in UC. Therefore, the goal of this study was to evaluate the expression of PD-1 and PD-L1 in canine UC cell lines and PD-1 on lymphocytes from peripheral blood and urine of dogs with UC.
Methods
Three canine UC cell lines were evaluated for the presence of PD-1 and PD-L1 expression via western blot, flow cytometry, and fluorescence microscopy. The presence of PD-1 on lymphocytes from peripheral blood and urine was evaluated via flow cytometry in 10 dogs with UC, 10 healthy control dogs, and 4 dogs with urinary tract infections.
Results
PD-1 and PD-L1 expression were detected in all 3 cell lines. Lymphocyte PD-1 expression was increased 2.4-fold on CD8+ T-cells in the urine of dogs with UC compared to healthy dogs (p=0.0006). Dogs with UC had a trend towards increased T-regulatory cells in both blood and urine compared to healthy control dogs (p=0.11).
Conclusion
Detection of PD-1/PD-L1 in canine UC cell lines and the upregulated expression in canine clinical patients supports future work as a possible therapeutic target in UC.
Funding Information
Funding for this project was provided by the OVC Pet Trust.