Spatial Transcriptomic Landscape of Canine Oral Squamous Cell Carcinoma
Canine Oral Squamous Cell Carcinoma (COSCC) is the second most common oral tumor in dogs, and the most relevant for comparative human trials as a spontaneous large animal model of disease. Thus, complete knowledge of the genomic landscape is essential for identifying therapeutic vulnerabilities and early biomarkers of disease across species. Historical genomic work has focused primarily on bulk sequencing, with only one publication using a laser capture dissection technique. The present study describes the complete molecular landscape of COSCC with spatial distinction between the surface tumor, deep invasive front, tumor microenvironment, and peritumoral dysplasia compared to matched normal samples. Each region demonstrated distinct molecular signatures. Genes related to epithelial growth factor (EGFR) and epithelial mesenchymal transformation (EMT) were upregulated in peri-tumoral dysplasia and surface cancer. Additionally, KRAS, SSP1 and KRT14 were upregulated in cancer, therefore combining these read outs may be useful in differentiating high grade dysplasia from malignant tissue at a molecular level. The primary tumor infiltrating leukocyte present in the tumor stroma were M2 macrophages. IL-10 expression was also significantly higher in the stroma, suggesting that tumor associated macrophages were directly related to establishing an immunosuppressive environment via cytokine secretion. The other predominant leukocytes were T-cells, with CD4+ T-cells being most common. CD4+ T cells expressed transcripts for both stimulatory (adaptive immunity with B cells and ICOS) and inhibitory molecules (CTLA4). However, the observed increase in CTLA4 suggests that this inhibitory signal may be preventing a robust anti-tumor immune response representing a therapeutic target for COSCC. Overall design: Spatial transcriptomic analysis of canine oral squamous cell carcinoma and non-malignant tissues was performed on the NanoString GeoMx Digital Spatial Profiler platform utilizing the GeoMx Canine Cancer Atlas assay to assess the expression of 1,962 genes