M1 macrophage recruitment correlates with worse outcome in SHH Medulloblastomas

Chanhee Lee,Ji Hoon Phi,Kyu-Chang Wang,Se Hoon Kim,Sung-Hye Park,Joongyub Lee,Ji Yeoun Lee,Seung-Ki Kim,Seung Ah Choi

doi:10.1186/s12885-018-4457-8

Abstract

BackgroundRecent 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.MethodsMolecular 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.ResultsTAM (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.ConclusionM1 rather than M2 correlates more strongly with worse outcome in SHH medulloblastoma.

Highlights

Recent progress in molecular analysis has advanced the understanding of medulloblastoma (MB) and is anticipated to facilitate management of the disease
We identified 5 Wingless/ Integrated (WNT), 16 Sonic hedgehog (SHH), 5 Group3, and 26 Group4 MBs through class prediction analysis (Additional file 1: Figure S2); 7 of the 16 patients identified as SHH subgroup had adequate formalin-fixed paraffin-embedded (FFPE) tissue samples available
Activated macrophage recruitment in the medulloblastoma subgroups First, we investigated the unique recruitment pattern of tumor-associated macrophages (TAM) in the different MB subgroups

Summary

Introduction

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; the functional role of their activated phenotype (M1/M2) remains controversial. We investigate the correlation between tumor-associated macrophage (TAM) recruitment within the MB subgroups and prognosis. Progress in molecular diagnostics has revealed that MB is classified into 4 subgroups: WNT, SHH, Group 3 (G3) and Group 4 (G4) [1, 2, 4]. The significance of lymphocytes and tumor-associated macrophages (TAMs) in the tumor microenvironment has been perpetually examined for more than a decade; their comprehensive role is rather elusive [8,9,10,11,12]. It has been commonly accepted that classically activated M1 macrophages suppress tumor growth and progression by production of reactive oxygen species (e.g., nitric oxide), whereas alternatively activated M2

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Conclusion