Defining the extracellular matrix for targeted immunotherapy in adult and pediatric brain cancer

Day, ZI; Roberts-Thomson, S; Nouri, YJ; Dalton, NS; Wang, SS; Davenport, A; Ludlow, LE; Hulett, MD; Cross, RS; Jenkins, MR

Author(s): Day, ZI; Roberts-Thomson, S; Nouri, YJ; Dalton, NS; Wang, SS; Davenport, A; Ludlow, LE; Hulett, MD; Cross, RS; Jenkins, MR;
Details: Publication Year 2025-06-14,Volume 9,Issue #1,Page 184
Journal Title: NPJ Precision Oncology
Abstract: High-grade gliomas (HGGs), including glioblastoma (GBM) and pediatric diffuse midline gliomas (DMGs), remain highly fatal despite therapeutic advances. The tumor microenvironment (TME), particularly the extracellular matrix (ECM), plays a crucial role in tumor progression, immune exclusion, and drug resistance. We performed a comprehensive proteomic, transcriptomic, and pathological characterization of the ECM in primary adult and pediatric HGGs. Using cell surface proteomics, TCGA transcriptomics, and immunohistochemistry, we identified key ECM components influencing immune infiltration. We integrated these findings into ImmunoTar, a computational model prioritizing immunotherapeutic targets. Our study presents the first in-depth cell surface proteomic landscape of HGG ECM, identifying CSPG4/5, PTPRZ1, SDC1, TGFBR3, PLG, and GPC2 as key targets. We validate ECM-targeted CAR T cell therapy, including Glypican-2 (GPC2), which shows strong efficacy against pediatric DIPG. These findings highlight ECM-focused immunotherapy as a promising strategy to overcome HGGs' immunosuppressive TME, particularly in pediatric patients.
Publisher: Springer Nature
Research Division(s): Personalised Oncology
PubMed ID: 40517137
Publisher's Version: https://doi.org/10.1038/s41698-025-00956-z
Open Access at Publisher's Site: https://doi.org/10.1038/s41698-025-00956-z.
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-06-26 09:55:16

Last Modified: 2025-06-26 09:56:13