Characterization of the Tumor Microenvironment in Jaw Osteosarcomas, towards Prognostic Markers and New Therapeutic Targets

SIMPLE SUMMARY: Jaw osteosarcoma (JO) differs from its long-bones counterpart in many ways. The pathophysiology of this disease is still unknown, but the tumor microenvironment seems to play an important role in the progression of the disease and might offer new therapeutic perspectives. Through an immunohistochemical study performed on 50 biopsies of JO, we investigated various parameters associated with bone resorption, vascular and immune infiltrates. We demonstrated a strong and significant correlation between CD163 staining and lower survival in patients. Also, high levels of RANK and RANKL were found in the tumor samples and correlated with lower disease-free survival, while the T cells markers (CD4(+) and CD8(+)) and the immune checkpoint PD-1/PD-L1 were poorly detected in the samples. ABSTRACT: Background—The purpose of this study was to investigate the bone resorption, as well as the vascular and immune microenvironment, of jaw osteosarcomas (JO) and to correlate these features with patient clinical outcomes. Methods—We studied 50 JO biopsy samples by immunohistochemical analysis of tissue microarrays (TMAs). We investigated the bone remodeling markers RANK/RANKL/OPG, the endothelial glycoprotein CD146, and biomarkers of the immune environment (CD163 and CD68 of macrophages, CD4+ and CD8+ of tumor-infiltrating lymphocytes (TILs), and an immune checkpoint PD-1/PD-L1). The biomarkers were analyzed for their influence on progression (recurrence and metastasis), overall survival (OS), and disease-free survival (DFS). Results—A strong and significant correlation has been found between CD163 staining and lower OS and DFS. The level of CD4+ and CD8+ staining was low and non-significantly associated with survival outcomes. High levels of RANK and RANKL were found in the tumor samples and correlated with lower DFS. Conclusion—Our findings suggest that CD163+ TAMs represent markers of poor prognosis in JO. Targeting TAMs could represent a valuable therapeutic strategy in JO.