Metastatic Immune Infiltrates Correlate with Those of the Primary Tumor in Canine Osteosarcoma.

Our lack of understanding of the immune microenvironment in canine osteosarcoma (cOSA) has limited the identification of potential immunotherapeutic targets. In particular, our ability to utilize readily available tissue from a dog's primary tumor to predict the type and extent of immune response in their pulmonary metastatic lesions is unknown. We therefore collected 21 matched pairs of primary tumors and pulmonary metastatic lesions from dogs with OSA and performed immunohistochemistry to quantify T lymphocyte (CD3), FOXP3+ cell, B lymphocyte (Pax-5), and CD204+ macrophage infiltration. We found that T lymphocytes and FOXP3+ infiltrates in primary tumors positively correlated with that of metastatic lesions (ρ= 0.512, P= 0.038 and ρ= 0.698, P= 0.007, respectively), while a strong trend existed for CD204+ infiltrates (ρ= 0.404, P= 0.087). We also observed T and B lymphocytes, and CD204+ macrophages to be significantly higher in a dog's pulmonary metastasis compared to their primary tumor (P= 0.018, P= 0.018, P= 0.016, respectively), while FOXP3+ cells were only significantly higher in metastases when all primary tumor and metastasis lesions were compared without pairing (P= 0.036). Together, these findings suggest the metastatic immune microenvironment may be influenced by that of the primary cOSA, and that primary tumor immune biomarkers could potentially be applied to predict immunotherapeutic responses in gross metastatic disease. We therefore provide a rationale for the treatment of cOSA pulmonary metastases with immunotherapeutics that enhance the anti-tumor activity of these immune cells, particularly in dogs with moderate to high immune cell infiltration in their primary tumors. This article is protected by copyright. All rights reserved.