Zhang Jin, Yuan Xia, Wang Yuan, Liu Jingjing, Li Zhigang, Li Shuting, Liu Yan, Gong Xiaojun, Sun Yanling, Wu Wanshui, Sun Liming, Du Shuxu, Wang Tianyou
Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Disease in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
Front Oncol. 2022 Jul 4;12:893132. doi: 10.3389/fonc.2022.893132. eCollection 2022.
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.
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.
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 ( = 0.038, HR = 0.241) and M1 macrophages ( = 0.034, HR = 0.333) with good 5-year progression-free survival (PFS); however, M2 macrophages had no correlation with survival of medulloblastoma patients (> 0.05).
High percentage of total macrophages and M1 macrophages are correlated with good outcome of medulloblastoma patients. TAMs might be a target of therapy.
巨噬细胞极化在脑肿瘤的肿瘤微环境中起着至关重要的作用。然而，肿瘤相关巨噬细胞（TAM）在髓母细胞瘤中的作用仍存在争议。因此，我们研究了巨噬细胞在髓母细胞瘤组织中的分布，并分析了TAM募集与髓母细胞瘤患者预后的相关性。
我们共获取了71例髓母细胞瘤患者的石蜡切片，采用多重荧光免疫组化方法，用针对CD68、HLA-DR和CD163的单克隆抗体检测活化表型（M1/M2）。使用InForm软件对极化巨噬细胞的数量进行定量。根据临床数据和定量的巨噬细胞数据分析预后。
研究表明，在音猬因子（SHH）髓母细胞瘤中TAM显著高于其他亚组，转移组中的M1巨噬细胞显著高于非转移组。Kaplan-Meier生存分析和多变量Cox回归模型显示，总巨噬细胞高比例（=0.038，HR=0.241）和M1巨噬细胞高比例（=0.034，HR=0.333）与5年无进展生存期（PFS）良好相关；然而，M2巨噬细胞与髓母细胞瘤患者的生存无相关性（>0.05）。
总巨噬细胞和M1巨噬细胞的高比例与髓母细胞瘤患者的良好预后相关。TAM可能是一个治疗靶点。
