Language

English

Publication Date

11-23-2025

Journal

EBioMedicine

DOI

10.1016/j.ebiom.2025.106043

PMID

41285059

PMCID

PMC12681837

PubMedCentral® Posted Date

11-23-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Background: 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.

Methods: 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.

Findings: 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 Ratiolow vs high 2.19 [95% CI 1.197-4.016]), while M2 macrophages (HRlow vs high 0.50 [95% CI 0.250-1.003]), NK cells (HRlow vs high 0.40 [95% CI 0.207-0.792]), and B cells (HRlow 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 (HRlow 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 (HRhigh vs low 2.21 [95% CI 1.341-3.651]) and PFS (HRhigh vs low 2.15 [95% CI 1.28-3.61]).

Interpretation: 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.

Funding: 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).

Keywords

Medulloblastoma, Multiplex immunofluorescence, Tertiary lymphoid structures, Prognosis

Published Open-Access

yes

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