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

doi:10.3389/fonc.2022.893132

Tumor-Associated Macrophages Correlate With Prognosis in Medulloblastoma

Front Oncol. 2022 Jul 4:12:893132. doi: 10.3389/fonc.2022.893132. eCollection 2022.

Authors

Jin Zhang^{1

2}, Xia Yuan³, Yuan Wang¹, Jingjing Liu¹, Zhigang Li⁴, Shuting Li¹, Yan Liu¹, Xiaojun Gong¹, Yanling Sun¹, Wanshui Wu¹, Liming Sun¹, Shuxu Du¹, Tianyou Wang²

Affiliations

¹ Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
² 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.
³ State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.
⁴ Hematologic Disease Laboratory, 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 Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.

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.

Keywords: immunotherapy; macrophage; medulloblastoma; phenotype; prognosis.