Surfaceome Proteomic of Glioblastoma Revealed Potential Targets for Immunotherapy

• Published in: Frontiers in immunology Vol. 12; p. 746168
• Main Authors: Rose, Mélanie, Cardon, Tristan, Aboulouard, Soulaimane, Hajjaji, Nawale, Kobeissy, Firas, Duhamel, Marie, Fournier, Isabelle, Salzet, Michel
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers 27-09-2021; Frontiers Media S.A
• Series: Frontiers in Immunology
• Subjects: Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Brain - metabolism; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Brain Neoplasms - therapy; Cell Line, Tumor; Clinical Trials as Topic; Drug Discovery; drugs; glioblastoma; Glioblastoma - genetics; Glioblastoma - metabolism; Glioblastoma - therapy; Humans; immune therapy; Immunology; Immunotherapy - methods; Life Sciences; Membrane Proteins - antagonists & inhibitors; Membrane Proteins - chemistry; Membrane Proteins - genetics; Membrane Proteins - metabolism; Molecular Targeted Therapy; mutated proteins; Neoplasm Proteins - antagonists & inhibitors; Neoplasm Proteins - chemistry; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Protein Conformation; Proteomics - methods; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; surface proteins; surfaceome proteomic; immune therapy; surfaceome proteomic; glioblastoma; drugs; mutated proteins; surface proteins; clinical trials
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.746168

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.