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. 2025 Feb 17;38(2):55.
doi: 10.1007/s13577-025-01181-3.

Immunomodulatory role of exosome-derived content in pediatric medulloblastoma: a molecular subgroup perspective

Jessica Oliveira de Santis #  1   2 , Graziella Ribeiro de Sousa #  3   4 , Rosane Gomes de Paula Queiroz  5 , Marina Ferreira Cândido  3 , Fausto Almeida  6 , Caroline Patini de Rezende  6 , Patricia Cassia de Ruy  7 , Gabriel Santos Arini  8 , Beth Coyle  9 , Philippa Wade  9 , María Sol Brassesco  10 , Carlos Alberto Scrideli  5   3 , Luiz Gonzaga Tone  5 , Elvis Terci Valera  5
Affiliations

Immunomodulatory role of exosome-derived content in pediatric medulloblastoma: a molecular subgroup perspective

Jessica Oliveira de Santis et al. Hum Cell. .

Abstract

Medulloblastoma (MB) is the most common malignant brain tumor in children, comprising four distinct subgroups: wingless (WNT), sonic hedgehog (SHH), Group 3, and Group 4. MYC amplification and metastatic dissemination are challenges in clinical management, and tumor-associated macrophages (TAMs) play an essential role in these intricate molecular processes. However, the influence of immune cells in MB metastasis and MYC-amp is unclear. Secretion of extracellular vesicles (EVs) has emerged as a pivotal mediator facilitating communication within the tumor microenvironment, orchestrating coordinated responses among immune cells during tumor initiation, progression, and tumor dissemination. Here, we sought to elucidate the role of exosome-derived MBs in promoting specific patterns of TAM polarization across different molecular subgroups of MB cell lines. CIBERSORTx analysis using a single-cell RNA dataset revealed an increase in M0 macrophages and a decreased proportion of M2 macrophages in MB patients with tumor dissemination in the central nervous system (CNS). Cell-derived exosomes were found to secrete high levels of IL-4, IL-10, and TGF-β, indicative of a protumor M2-profile pattern. Moreover, EVs from SHH TP53-mutated, Group 3/4, and MYC-amplified MBs induced dissimilar patterns of TNF-α and/or IL-1β overexpression. This study demonstrates that exosomes from pediatric MBs promote a predominant M2-macrophage phenotype and Group 3, Group 4, SHH TP53-mutated, and MYC-amplified MBs induced a mixed M1/M2 response pattern. These findings shed light on the pivotal role of exosomes in modulating the immune response, potentially contributing to immune escape in this malignant neoplasm.

Keywords: Biomarkers; Children; Extracellular vesicles; Medulloblastoma; Tumor progression.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare that they have no competing interests. Ethical approval: The study was conducted in accordance with the CEUA of the Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil (CEUA-FMRP, Protocol number: 2.101.529).

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