Presentation Authors: Suraj Pursnani*, Damini Chand, Bronx, NY, Deepika Dhawan, West Lafayette, IN, Alexander Sankin, Xiaoxin Ren, Juan Lin, Mark Schoenberg, Bronx, NY, Deborah W. Knapp, West Lafayette, IN, Xingxing Zang, Bronx, NY
Introduction: Canine bladder cancer provides a novel model system for the study of invasive human urothelial carcinoma. The immunobiology of canine tumors is largely unknown. We report the first evaluation of immune checkpoint B7x, a major contributor to T-cell co-inhibition in human bladder cancers, in primary canine urothelial neoplasms.
Methods: Canines with spontaneous bladder cancer were identified and tumor specimens were collected by cystoscopic biopsy from treatment-naive dogs. Normal bladder tissue was collected from dogs that were being euthanized for conditions other than bladder-related diseases. RNA-seq data from 29 canine invasive bladder tumors and 4 normal bladders were used to determine B7x expression. Gene ontology was performed to explore the biological role of B7x. A set of 50 canine bladder tumor samples and 4 normal bladder tissues were evaluated for B7x protein by IHC and corresponding clinicopathologic data was obtained from chart review. TCGA and GTEx were used to examine B7x expression in 599 human urothelial tumors (BLCA).
Results: Of the 50 canine urothelial tumors, 47 (94%) were stage pT2 or higher and 43 (86%) were non-metastatic. In the RNA-seq analysis, B7x expression in the tumors was 5.72 and 7.04 fold up-regulated, respectively, using DESeq2 and edge R (Figure 1). IHC analysis revealed 30 of 50 cases as positive for B7x expression. B7x intensity was scored as negative in 40%, low in 24%, medium in 14% and high in 22% of cases (an example of high B7x expression is seen in Figure 2). There was no correlation between B7x expression and clinicopathologic characteristics. B7x expression was closely associated with immune processes in gene ontology analysis. In human BLCA, B7x expression was significantly associated with worse overall survival (p=0.02).
Conclusions: Our results suggest that B7x is highly expressed in canine bladder cancer, which is a tumor model that is vital to advancing the translational research on B7x, a new potential therapeutic target in human bladder cancer.
Source of Funding: D. Chand is supported by the Thanks to Scandinavia/Borge endowment. This work was supported by NIH R01CA175495 and R01DK100525 (X. Zang).