Surfaceome Proteomic of Glioblastoma Revealed Potential Targets for Immunotherapy

Frontiers in Immunology

Nawale Hajjaji¹  Firas Kobeissy²  Isabelle Fournier³  Michel Salzet³  Tristan Cardon⁴  Mélanie Rose⁴  Marie Duhamel⁴  Soulaimane Aboulouard⁴ 

[1] Breast Cancer Unit, Oscar Lambret Center, Lille, France;Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon;Institut Universitaire de France, Paris, France;Université Lille, Inserm, CHU Lille, U1192, Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse (PRISM), Lille, France;

关键词: surfaceome proteomic;    glioblastoma;    immune therapy;    surface proteins;    mutated proteins;    drugs;   

DOI  :  10.3389/fimmu.2021.746168

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown