Immune Checkpoint B7x (B7-H4/B7S1/VTCN1) is Over Expressed in Spontaneous Canine Bladder Cancer: The First Report and its Implications in a Preclinical Model

Background: B7x (B7-H4/B7S1/VTCN1), an inhibitory immune checkpoint molecule is a potential therapeutic target owing to its immunosuppressive effect and well-known expression in cancers. Immune checkpoints in canine bladder cancer are largely undefined. Here, we report the first evaluation on expression of B7x in spontaneous canine invasive bladder cancer, a novel model system for the study of invasive human urothelial carcinoma. Objective: This work aims to study expression of immune checkpoint B7x in spontaneous canine invasive bladder cancer. Methods: RNA-seq analysis was performed to determine B7x expression in tumor versus normal bladder. Gene ontology (GO) study was used to explore the biological role of B7x. B7x protein expression was evaluated by immunohistochemistry (IHC). TCGA and GTEx were used to examine B7x expression in 599 human bladder urothelial carcinoma (BLCA). Results: RNA-seq analysis indicated 5.72 and 7.04 fold up regulation of B7x in tumors, using DESeq2 and edge R respectively (p