Breed-Associated Differences in Differential Gene Expression Following Immunotherapy-Based Treatment of Canine High-Grade Glioma

Canine high-grade glioma (HGG) is a deadly disease in dogs, with limited treatment options. Involving the host immune system in the fight against HGG through immunotherapy has improved outcomes in many dogs, with a notable exception in the French bulldog breed. We hypothesized that French bulldog HGG responds differently to immunotherapy than other breeds, and that this response difference is attributable to differences in transcriptomic landscapes in the breed compared to other breeds. We performed bulk RNA sequencing (RNASeq) on tumors pre-treatment and post-treatment and examined the differentially expressed genes (DEGs) between the two timepoints in both French bulldogs and in our comparison group of boxers and Boston terriers. We then analyzed the differences in DEGs between French bulldogs and boxers and Boston terriers, and performed gene set enrichment analysis (GSEA) to categorize the observed changes by gene function. We confirmed that when compared to boxers and Boston terriers, the transcriptomes of French bulldog tumors change in significantly different ways following immunotherapy treatment, with many DEGs mapping to tumor-promoting pathways and immune pathways. This study highlights important breed-associated differences in HGG transcriptomes, which may guide patient-centered immunotherapy treatment to improve patient outcomes.