Characterizing tumor-associated macrophage behavior in the tumor microenvironment of canine osteosarcoma
Yang, Katherine
2023
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Canine osteosarcoma (OS) is an aggressive cancer with a strong predilection for lung metastasis within a year after diagnosis and starting standard therapy (surgery and chemotherapy). Recent research focusing on the role of immune cells in the tumor microenvironment identified macrophages as having an important role in supporting tumor growth and creating an immunosuppressive environment. Subsequent ... read moreclinical trials in dogs with OS using immunotherapy combinations designed to target the immune microenvironment have shown evidence of activity, but it is unknown how macrophage activity changes in dogs between the primary tumor and development of metastatic disease in the lungs. M1 macrophages are classically considered to have anti-tumor effects, while M2 macrophages are associated with pro-tumor responses. Therefore, it is hypothesised that companion dogs with naturally occurring OS will have a higher macrophage infiltration with immunosuppressive signatures in lung metastases compared to the primary tumor. It is also predicted that these immunosuppressive signatures will be associated with disease-free interval and an M2 phenotype. To begin to characterise the macrophage phenotype in canine OS, RNA was extracted from patient-matched primary and pulmonary metastatic tissues to obtain differential gene expression signatures using the Nanostring nCounter CanineIO panel. Patient-matched formalin-fixed tissue was evaluated using the GeoMx digital spatial profiler to evaluate macrophage infiltration and associated gene expression changes. Briefly, CD163 was used to help identify macrophages in each tissue section, and macrophages and associated tumor cells were collected for library preparation and sequenced individually. Regions of interest were evaluated for degree of macrophage infiltration, and gene expression signatures were determined and correlated with progression-free survival. Additional comparisons of macrophage and tumor-associated signatures will be completed between patient-matched primary and pulmonary metastatic lesions. These findings will provide valuable information on macrophage behavior in the canine OS microenvironment and may identify outcome- associated biomarkers for future prospective validation.
Cummings School of Veterinary Medicine Summer Student Research 2023.read less - ID:
- xp68kx29h
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