Tumor-Associated Macrophages Correlate With Prognosis in Medulloblastoma
Jin Zhang, Xia Yuan, Yuan Wang, Jingjing Liu, Zhigang Li, Shuting Li, Yan Liu, Xiaojun Gong, Yanling Sun, Wanshui Wu, Liming Sun, Shuxu Du, Tianyou Wang
Abstract
Purpose Macrophage polarization plays an essential role in the tumor microenvironment of brain tumors. However, the role of tumor-associated macrophages (TAMs) in medulloblastoma still remains controversial. Thus, we investigated the distribution of macrophages in medulloblastoma tissues and analyzed the association of TAM recruitment and medulloblastoma patients’ outcomes. Methods We obtained a total of 71 paraffin sections from patients with medulloblastoma, and detected the activated phenotype (M1/M2) by monoclonal antibodies for CD68, HLA-DR and CD163 with multiple fluorescence immunohistochemistry method. The number of polarized macrophages was quantified using the InForm software. Outcomes were analyzed according to clinical data and quantified macrophage data. Results The study revealed that TAMs were significantly higher in sonic hedgehog (SHH) medulloblastoma than in other subgroups, and M1 macrophages in metastatic group were significantly higher than those in non-metastatic group. A Kaplan-Meier survival analysis and multivariate Cox regression model showed the correlation of high percentage of total macrophages ( P = 0.038, HR = 0.241) and M1 macrophages ( P = 0.034, HR = 0.333) with good 5-year progression-free survival (PFS); however, M2 macrophages had no correlation with survival of medulloblastoma patients ( P > 0.05). Conclusion High percentage of total macrophages and M1 macrophages are correlated with good outcome of medulloblastoma patients. TAMs might be a target of therapy.