M1 Macrophage Recruitment Correlates with Worse Outcome in SHH Medulloblastoma

Abstract

Background. Recent progress in molecular analysis has advanced the understanding of medulloblastoma (MB) and it is anticipated to help the management of the disease. It is revealed to be comprised of 4 molecular subgroups: WNT, SHH, Group 3, and Group 4. Macrophage has been suggested to play a crucial role in tumor microenvironment, however functional role of their activated phenotype (M1/M2) is still controversial. Herein, we investigate the correlation between tumor-associated macrophages (TAM), both M1 and M2 macrophages, within MB subgroups and the prognosis.

Methods. Molecular subgrouping was performed by nanoString-based RNA assay on retrieved snap-frozen tissue samples. Immunohistochemistry (IHC) and immunofluorescence (IF) assay were performed on subgroup identified samples and number of polarized macrophages were quantified from IHC. Survival analyses were conducted with collected clinical data and quantified macrophage data.

Results. TAM (M1/M2) recruitment in SHH MB was significantly higher compared to other subgroups. Kaplan-Meier survival curve and multivariate cox regression demonstrated that high M1 expressers show worse overall survival (OS) and progression-free survival (PFS) than low expressers in SHH MB with relative risk (RR) of 11.918 and 6.022 , respectively.

Conclusion. M1 rather than M2 correlates better with worse outcome in SHH medulloblastoma.