Profiling tumour-infiltrating immune cells in a large paediatric medulloblastoma cohort: a retrospective analysis.

Abstract

Tumour-infiltrating immune cells exert both pro-tumour and anti-tumour effects on intracranial tumours. In this study, we investigated the prognostic value of various infiltrating immune cells in medulloblastoma (MB) within a large cohort. We employed multiplex immunofluorescent (mIF) staining of tissue microarrays to assess the densities of T cells, B cells, NK cells, macrophages, and immune checkpoints in tumour samples from 249 primary paediatric patients with primary MB. Overall survival (OS) analysis, progression-free survival (PFS), and Cox regression analyses were utilised to explore potential relationships between immune cell densities and survival outcomes. Subsequently, multivariate Cox regression was validated using an external database. Significant differences in the immune microenvironment among molecular groups of MB and their prognostic implications were observed. CD4+ T cell infiltration was positively correlated with improved OS prognosis (Hazard Ratio^{low vs high} 2.19 [95% CI 1.197-4.016]), while M2 macrophages (HR^{low vs high} 0.50 [95% CI 0.250-1.003]), NK cells (HR^{low vs high} 0.40 [95% CI 0.207-0.792]), and B cells (HR^{low vs high} 0.51 [95% CI 0.291-0.902]) were associated with poorer PFS prognosis. We detected the presence of early tertiary lymphoid structures in MB. The infiltration of B cells (HR^{low vs high} 0.50 [95% CI 0.271-0.941]) correlated with poorer OS. The prognostic significance of B cells was further corroborated in cases from external data. Additionally, multivariate Cox regression confirmed that B cells were identified as independent negative prognosticators for OS (HR^{high vs low} 2.21 [95% CI 1.341-3.651]) and PFS (HR^{high vs low} 2.15 [95% CI 1.28-3.61]). Our study provides a comprehensive characterisation of the spatial distribution of certain immune cells and tumour cells within the tumour core of patients with various subtypes of MB, underscoring the prognostic significance of B cells in these individuals. Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes (PWD & RPP-MRI: JYY2018-7); National Natural Science Foundation of China (32300773); China Postdoctoral Science Foundation (2022M721864).