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Polarization and Characterization of M1 and M2 Human Monocyte-Derived Macrophages on Implant Surfaces
Published on: December 6, 2024
M1 macrophage recruitment correlates with worse outcome in SHH Medulloblastomas
Chanhee Lee1, Joongyub Lee2, Seung Ah Choi1
1Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, 101 Daehakro, Jongno-gu, 110-744, Seoul, Republic of Korea.
Background:
Recent progress in molecular analysis has advanced the understanding of medulloblastoma (MB) and is anticipated to facilitate management of the disease. MB is composed of 4 molecular subgroups: WNT, SHH, Group 3, and Group 4. Macrophages play a crucial role in the tumor microenvironment; however, the functional role of their activated phenotype (M1/M2) remains controversial. Herein, we investigate the correlation between tumor-associated macrophage (TAM) recruitment within the MB subgroups and prognosis.
Methods:
Molecular subgrouping was performed by a nanoString-based RNA assay on retrieved snap-frozen tissue samples. Immunohistochemistry (IHC) and immunofluorescence (IF) assays were performed on subgroup identified samples, and the number of polarized macrophages was quantified from IHC. Survival analyses were conducted on collected clinical data and quantified macrophage data.
Results:
TAM (M1/M2) recruitment in SHH MB was significantly higher compared to that in other subgroups. A Kaplan-Meier survival curve and multivariate Cox regression demonstrated that high M1 expressers showed worse overall survival (OS) and progression-free survival (PFS) than low M1 expressers in SHH MB, with relative risk (RR) values of 11.918 and 6.022, respectively.
Conclusion:
M1 rather than M2 correlates more strongly with worse outcome in SHH medulloblastoma.
Insights
In medulloblastoma, high M1 macrophage levels correlate with worse outcomes in the SHH subgroup. This finding suggests M1 macrophages, not M2, are key indicators of prognosis in SHH medulloblastoma.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Medulloblastoma (MB) comprises four molecular subgroups: WNT, SHH, Group 3, and Group 4.
- Tumor-associated macrophages (TAMs) are key components of the tumor microenvironment, but their M1/M2 polarized states' roles in MB are unclear.
Purpose of the Study:
- To investigate the correlation between TAM recruitment within medulloblastoma subgroups and patient prognosis.
- To determine the differential impact of M1 and M2 macrophage phenotypes on outcomes in SHH medulloblastoma.
Main Methods:
- Molecular subgrouping of MB tissues using a nanoString-based RNA assay.
- Quantification of M1 and M2 TAMs via immunohistochemistry (IHC) and immunofluorescence (IF).
- Survival analysis using Kaplan-Meier curves and Cox regression on clinical and macrophage data.
Main Results:
- TAM recruitment was significantly higher in the SHH medulloblastoma subgroup compared to others.
- High M1 TAM expression in SHH MB was associated with significantly worse overall survival (OS) and progression-free survival (PFS).
- Relative risk for worse OS and PFS was notably high (11.918 and 6.022, respectively) in patients with high M1 expression.
Conclusions:
- The M1 macrophage phenotype, not M2, is strongly associated with poorer outcomes in SHH medulloblastoma.
- M1 TAM levels serve as a significant prognostic biomarker for SHH medulloblastoma.
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