Prognostic and Predictive Value of CD163+ Macrophages for Neoadjuvant Chemotherapy in Osteosarcoma

Background: The CD163+ macrophage is considered a key component of the tumor immune microenvironment (TIME) in osteosarcoma (OS) in relation to tumor progression and chemotherapy resistance. However, the relationship between CD163+ macrophage infiltration and the efficacy of neoadjuvant chemotherapy (NACT) in OS remains unexplored. Methods: This study collected a total of 195 biopsy samples from newly diagnosed, pretreated OS patients. The infiltration of CD163+ macrophages was evaluated using immunohistochemical (IHC) staining with anti-CD163 antibody. Additionally, multiplex fluorescence staining (CD8, CD68, CD163, and PDL1) was employed to further characterize the TIME profiles associated with different levels of CD163+ macrophage infiltration. The relationships between various clinical characteristics, survival outcomes, and CD163+ macrophage infiltration levels were also assessed. Results: CD163+ macrophages in biopsy tissues ranged from 2.25 cells/mm2 to 3974.79 cells/mm2 and 1.37 cells/mm2 to 3027.20 cells/mm2 in the training and validation cohorts respectively. Multivariate analysis identified that CD163+ macrophage density was an independent predictor for NACT response. Importantly, patients with high CD163+ macrophage infiltration exhibited poorer DFS, DMFS, and RFS than their counterparts. Conclusions: CD163+ macrophage infiltration was an independent predictor for NACT response. Patients with high CD163+ macrophage density benefited less from NACT and exhibited a more immunosuppressive TIME than low-density patients.