Mif-CD74 Signaling Drives Immune Modulation in Medulloblastoma

Authors

• Benjamin Draper
• Zhen You
• Dean Thompson
• Xu Guo
• Alaide Morcavallo
• Diego Chillon Pino
• Carlos Lorenzo Gido Nery
• Sumana Shrestha
• Chantelle E Bowers
• Courtney Himsworth
• Alberto Delaidelli
• Bethany Remeniuk
• Sonia Morlando
• Brandon Wade
• Freya Gordon
• Yara Sanchez-Corrales
• Bei Hopkins
• Natalie Monteiro
• Darren Locke
• Miao Liu
• Jacob Torrejon Diaz
• Kevin Greenslade
• Barbara Martins da Costa
• Karen Barker
• Colin Kwok
• Olumide Ogunbiyi
• Anya Fletcher
• Stacey Richardson
• Carlos Custodia
• Rafael Roque
• Thomas Jackson
• Regan Barfoot
• Sergi Castellano
• Rebecca M Hill
• Olivier Saulnier
• Thomas S Jacques
• Michael D Taylor
• Claudia C Faria
• Olivier Ayrault
• Poul H Sorensen
• John Anderson
• Louis Chesler
• L Frank Huang
• Steven C Clifford
• Laura K Donovan

Language

English

Publication Date

5-1-2026

Journal

Neuro-Oncology

DOI

10.1093/neuonc/noag020

PMID

41652893

PMCID

PMC13186457

PubMedCentral® Posted Date

2-6-2026

PubMedCentral® Full Text Version

Post-print

Abstract

Background: Relapsed medulloblastoma remains a significant therapeutic challenge as it is near universally fatal. The tumor microenvironment of medulloblastoma plays a critical role in tumor progression, influencing tumor growth, immune evasion, and therapeutic resistance. We hypothesized that defining tumor-immune interactions in diagnostic and relapsed medulloblastoma may uncover mechanisms of immune evasion and identify novel therapeutic targets.

Methods: We analyzed paired primary and recurrent RNA-sequencing data from 140 medulloblastoma patients to profile immune cell composition and validate spatial relationships within the TME. To identify key tumor-immune interactions, we developed a novel algorithm to detect receptor-ligand pairs using single-cell RNA-sequencing data. These interactions were validated across RNA and proteomic datasets. Their functional significance was empirically demonstrated in newly developed immunocompetent models of recurrent medulloblastoma that closely recapitulate the human disease.

Results: We observed a shift toward a heightened immunosuppressive TME at relapse. Using our algorithm, we identified biologically significant receptor-ligand interactions, most notably MIF-CD74, constitutively expressed at RNA and protein levels across medulloblastoma subgroups, at diagnosis and relapse. Disrupting MIF-CD74 interactions led to significant alterations in the tumor microenvironment, highlighting its functional significance.

Conclusions: Our multifaceted approach identified key tumor-immune interactions in medulloblastoma. Among these, MIF-CD74 was validated as a targetable interaction, demonstrating the utility of our integrative approach for identifying novel therapeutic targets across multiple tumor types.

Keywords

Humans, Medulloblastoma, Antigens, Differentiation, B-Lymphocyte, Macrophage Migration-Inhibitory Factors, Cerebellar Neoplasms, Histocompatibility Antigens Class II, Signal Transduction, Tumor Microenvironment, Intramolecular Oxidoreductases, CD74, immune-suppression, macrophages, relapsed medulloblastoma, tumor-immune microenvironment

Published Open-Access

yes

Recommended Citation

Draper, Benjamin; You, Zhen; Thompson, Dean; et al., "Mif-CD74 Signaling Drives Immune Modulation in Medulloblastoma" (2026). Faculty, Staff and Students Publications. 7332.
https://digitalcommons.library.tmc.edu/baylor_docs/7332