O02 - Transcriptional Profiling of the Immune Tumor Microenvironment in Canine Cutaneous Mast Cell Tumors

Abstract: Background – Canine cutaneous mast cell tumors (MCTs) are a common, yet clinically challenging tumor type given their variable biological behavior. While patients with histologically low-grade MCTs can often be effectively managed with surgery alone, the majority of those with high-grade MCTs succumb to their disease despite multimodal therapy. An improved understanding of the immune tumor microenvironment (TME) may help identify novel prognostic and therapeutic targets. Hypothesis/Objectives – The objective of this study was to interrogate the transcriptional profiles for differences in the immune TME between low- and high-grade MCTs. Animals – Twelve client-owned dogs with MCTs (6 Kiupel low-grade with clinically benign behavior and 6 Kiupel high-grade with clinically aggressive behavior) that underwent curative-intent surgery (Figure 1). Methods – Archived low- and high-grade cutaneous MCTs were retrospectively identified. Tumor grade was confirmed by a single veterinary pathologist. RNA was extracted from all tumors followed by immune transcriptional profiling (Nanostring Canine IO panel) and analysis (ROSALIND platform). Results – Immune transcriptional profiling identified 9 differentially expressed genes (p-adj < 0.05, Figure 2). Programmed cell death protein 1 (PDCD1) and inducible T-cell costimulator ligand (ICOSLG) gene expression were significantly higher in a subset of high-grade MCTs. Conclusions and clinical importance – Our data revealed significant differences in the immune transcriptome of low- and high-grade MCTs and provides early, pre-clinical rationale for targeting a subset of high-grade MCTs with immune checkpoint blockade. Efforts to confirm these findings on a protein level are ongoing.