Prognostic Impact of CD206+ M2-Like Macrophages in Canine Appendicular Osteosarcoma.

Abstract

A clear understanding of human and canine osteosarcoma (hOS and cOS) immunobiology is needed to develop effective immunotherapeutic strategies, a promising option to improve outcomes. Previous studies in humans and dogs have underscored the importance of the macrophagic infiltrate. Notably, high M2-like macrophage infiltration has been associated with increased metastatic progression-free survival in hOS treated with surgery and chemotherapy. Given the strong similarities between hOS and cOS, we hypothesized that tumour infiltration by M2-like macrophages would also be associated with an improved prognosis in dogs. Eighty-four dogs with a histological diagnosis of cOS were retrospectively selected from the database of five veterinary institutions and one pathology laboratory. Medical data and associated cOS samples were retrieved from electronic records and original pathology laboratories. Macrophage populations were identified by immunohistochemistry using anti-CD204 and anti-CD206 antibodies. Univariate and multivariate Cox proportional hazard models were performed to identify factors associated with overall survival time (OST) in dogs treated with surgery with (SOC) or without (SxOnly) adjuvant chemotherapy. In dogs treated surgically (SOC + SxOnly), only high CD206+ infiltrate was associated with longer OST in both univariate (p = 0.019) and multivariate analysis (p = 0.014). Within the SOC group, high CD206+ infiltrate (p = 0.006) and lower body weight (p = 0.029) were associated with better outcome in the univariate analysis while high CD206+ infiltrate (p = 0.003) and female sex (p = 0.044) were associated with a longer survival in the multivariate analysis. This observation underscores the role of M2-like macrophages in OS and strengthens the relevance of cOS as a model for hOS in the immunological field.