| Title: |
MIF-CD74 signaling drives immune modulation in medulloblastoma |
| Authors: |
Draper, Benjamin; You, Zhen; Thompson, Dean; Guo, Xu; Morcavallo, Alaide; Chillon Pino, Diego; Lorenzo Gido Nery, Carlos; Shrestha, Sumana; Bowers, Chantelle E; Himsworth, Courtney; Delaidelli, Alberto; Remeniuk, Bethany; Morlando, Sonia; Wade, Brandon; Gordon, Freya; Sanchez-Corrales, Yara; Hopkins, Bei; Monteiro, Natalie; Locke, Darren; Liu, Miao; Diaz, Jacob Torrejon; Greenslade, Kevin; Martins da Costa, Barbara; Barker, Karen; Kwok, Colin; Ogunbiyi, Olumide; Fletcher, Anya; Richardson, Stacey; Custodia, Carlos; Roque, Rafael; Jackson, Thomas; Barfoot, Regan; Castellano, Sergi; Hill, Rebecca M; Saulnier, Olivier; Jacques, Thomas S; Taylor, Michael D; Faria, Claudia C; Ayrault, Olivier; Sorensen, Poul H; Anderson, John; Chesler, Louis; Frank Huang, L; Clifford, Steven C; Donovan, Laura K |
| Contributors: |
Great Ormond Street Hospital Children’s Charity; NIHR Great Ormond Street Hospital Biomedical Research Centre, Mayo Clinic Foundation; Department of Defence (DoD) Peer Reviewed Cancer Research Program; Maya Dronca Foundation; Brains Together For A Cure, MRC Clinical Scientist Award, Cancer Research UK Discovery Programme Award; European Science Foundation; Little Hero, Children with Cancer UK; Children’s Cancer and Leukaemia Group; The Little Princess Trust; Stand Up 2 Cancer and Cancer Research UK |
| Source: |
Neuro-Oncology ; ISSN 1522-8517 1523-5866 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2026 |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1093/neuonc/noag020 |
| DOI: |
10.1093/neuonc/noag020/66801408/noag020.pdf |
| Availability: |
https://doi.org/10.1093/neuonc/noag020; https://academic.oup.com/neuro-oncology/advance-article-pdf/doi/10.1093/neuonc/noag020/66801408/noag020.pdf |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.2A823AAB |
| Database: |
BASE |