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Updated: Oct 17, 2025
Digital Spatial Profiling for Characterization of the Microenvironment in Adult-Type Diffusely Infiltrating Glioma
Published on: September 13, 2022
Surfaceome Proteomic of Glioblastoma Revealed Potential Targets for Immunotherapy
Mélanie Rose1, Tristan Cardon1, Soulaimane Aboulouard1
1Université Lille, Inserm, CHU Lille, U1192, Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse (PRISM), Lille, France.
Abstract:
Glioblastoma (GBM) is the most common and devastating malignant brain tumor in adults. The mortality rate is very high despite different treatments. New therapeutic targets are therefore highly needed. Cell-surface proteins represent attractive targets due to their accessibility, their involvement in essential signaling pathways, and their dysregulated expression in cancer. Moreover, they are potential targets for CAR-based immunotherapy or mRNA vaccine strategies. In this context, we investigated the GBM-associated surfaceome by comparing it to astrocytes cell line surfaceome to identify new specific targets for GBM. For this purpose, biotinylation of cell surface proteins has been carried out in GBM and astrocytes cell lines. Biotinylated proteins were purified on streptavidin beads and analyzed by shotgun proteomics. Cell surface proteins were identified with Cell Surface Proteins Atlas (CSPA) and Gene Ontology enrichment. Among all the surface proteins identified in the different cell lines we have confirmed the expression of 66 of these in patient's glioblastoma using spatial proteomic guided by MALDI-mass spectrometry. Moreover, 87 surface proteins overexpressed or exclusive in GBM cell lines have been identified. Among these, we found 11 specific potential targets for GBM including 5 mutated proteins such as RELL1, CYBA, EGFR, and MHC I proteins. Matching with drugs and clinical trials databases revealed that 7 proteins were druggable and under evaluation, 3 proteins have no known drug interaction yet and none of them are the mutated form of the identified proteins. Taken together, we discovered potential targets for immune therapy strategies in GBM.
Insights
Researchers identified novel cell-surface protein targets for glioblastoma (GBM) immunotherapy by comparing GBM and astrocyte cell surface proteins. This study reveals 11 specific potential targets, including mutated proteins, offering new avenues for GBM treatment strategies.
Area of Science:
- Neuro-oncology
- Proteomics
- Cancer immunotherapy
Background:
- Glioblastoma (GBM) is a highly aggressive brain tumor with poor patient outcomes.
- Existing treatments for GBM have limited efficacy, necessitating the discovery of new therapeutic targets.
- Cell-surface proteins are promising targets due to their accessibility and role in cancer signaling.
Purpose of the Study:
- To identify novel, GBM-specific cell-surface proteins for targeted therapies.
- To compare the surface proteome of GBM cells with that of normal astrocytes.
- To discover potential targets for immunotherapy and vaccine strategies in GBM.
Main Methods:
- Biotinylation of cell surface proteins in GBM and astrocyte cell lines.
- Shotgun proteomics for protein identification and quantification.
- Spatial proteomic analysis (MALDI-mass spectrometry) in patient tumors.
- Bioinformatic analysis including Gene Ontology enrichment and database matching.
Main Results:
- Identified 87 surface proteins overexpressed or exclusive to GBM cell lines.
- Confirmed expression of 66 surface proteins in patient glioblastoma samples.
- Discovered 11 specific potential GBM targets, including 5 mutated proteins (e.g., RELL1, CYBA, EGFR, MHC I).
- Seven identified targets are druggable and in clinical evaluation; three have no known drug interactions.
Conclusions:
- This study presents a comprehensive list of potential cell-surface targets for GBM.
- The identified targets, particularly mutated proteins, offer new opportunities for developing targeted immunotherapies and vaccines.
- The findings pave the way for novel therapeutic strategies against glioblastoma.
