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The PD-1 / PD-L1 pathway: possible immunotherapeutic target in canine urothelial carcinoma

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Title: The PD-1 / PD-L1 pathway: possible immunotherapeutic target in canine urothelial carcinoma
Author: Pinard, Christopher
Department: Department of Clinical Studies
Program: Clinical Studies
Advisor: Woods, PaulHocker, Samuel
Abstract: Canine urothelial carcinoma (UC) is the most common genitourinary tumour described in dogs. Despite the multitude of therapies attempted over the last decade, there continues to be a need for new and novel therapies to improve treatment response and overall survival. Additionally, given the advent of immunotherapy and checkpoint inhibitors in human muscle-invasive urothelial carcinoma, there remains a gap in knowledge regarding the immune landscape of canine urothelial carcinoma, especially pertaining to the programmed death ligand (PD-L1) and its receptor (PD-1). The present works evaluated three UC cell lines and documented protein and mRNA expression of both PD-1 and PD-L1 in all lines. In a group of canine patients with urothelial carcinoma, when compared to healthy control dogs, the CD8+ T lymphocyte expression of PD-1 was significantly elevated. Decreased CD8:Treg ratios were documented in the urine of UC patients, supportive of an immunosuppressive environment. Lastly, cytokines implicated in the upregulation of PD-1 were significantly elevated in UC patients when compared to healthy control dogs. This thesis provides evidence of tumour cell line- based expression of PD-1 and PD-L1, as well as the lymphocyte-specific expression of PD-1 in dogs with urothelial carcinoma. Therefore, we conclude that immune checkpoint therapy against PD-1 and/or PD-L1 should be further explored as a relevant therapeutic strategy in dogs with urothelial carcinoma.
Date: 2021-08
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Embargoed Until: 2022-09-01

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