CIITA-Transduced Glioblastoma Cells Uncover a Rich Repertoire of Clinically Relevant Tumor-Associated HLA-II Antigens.

Détails

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Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_848F6AADEDBE
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
CIITA-Transduced Glioblastoma Cells Uncover a Rich Repertoire of Clinically Relevant Tumor-Associated HLA-II Antigens.
Périodique
Molecular & cellular proteomics
Auteur⸱e⸱s
Forlani G., Michaux J., Pak H., Huber F., Marie Joseph E.L., Ramia E., Stevenson B.J., Linnebacher M., Accolla R.S., Bassani-Sternberg M.
ISSN
1535-9484 (Electronic)
ISSN-L
1535-9476
Statut éditorial
Publié
Date de publication
2021
Peer-reviewed
Oui
Volume
20
Pages
100032
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
CD4+ T cell responses are crucial for inducing and maintaining effective anticancer immunity, and the identification of human leukocyte antigen class II (HLA-II) cancer-specific epitopes is key to the development of potent cancer immunotherapies. In many tumor types, and especially in glioblastoma (GBM), HLA-II complexes are hardly ever naturally expressed. Hence, little is known about immunogenic HLA-II epitopes in GBM. With stable expression of the class II major histocompatibility complex transactivator (CIITA) coupled to a detailed and sensitive mass spectrometry-based immunopeptidomics analysis, we here uncovered a remarkable breadth of the HLA-ligandome in HROG02, HROG17, and RA GBM cell lines. The effect of CIITA expression on the induction of the HLA-II presentation machinery was striking in each of the three cell lines, and it was significantly higher compared with interferon gamma (IFNɣ) treatment. In total, we identified 16,123 unique HLA-I peptides and 32,690 unique HLA-II peptides. In order to genuinely define the identified peptides as true HLA ligands, we carefully characterized their association with the different HLA allotypes. In addition, we identified 138 and 279 HLA-I and HLA-II ligands, respectively, most of which are novel in GBM, derived from known GBM-associated tumor antigens that have been used as source proteins for a variety of GBM vaccines. Our data further indicate that CIITA-expressing GBM cells acquired an antigen presenting cell-like phenotype as we found that they directly present external proteins as HLA-II ligands. Not only that CIITA-expressing GBM cells are attractive models for antigen discovery endeavors, but also such engineered cells have great therapeutic potential through massive presentation of a diverse antigenic repertoire.
Mots-clé
Animals, Antigens, Neoplasm/immunology, Brain Neoplasms/immunology, Cattle, Cell Line, Tumor, Glioblastoma/immunology, Histocompatibility Antigens Class II/immunology, Humans, Nuclear Proteins/genetics, Nuclear Proteins/immunology, Peptides/immunology, Trans-Activators/genetics, Trans-Activators/immunology, Antigen discovery, Class II major histocompatibility complex transactivator, Glioblastoma, Immunopeptidomics
Pubmed
Web of science
Open Access
Oui
Financement(s)
Conseil Européen de la Recherche (ERC)
Création de la notice
09/10/2020 7:59
Dernière modification de la notice
23/11/2022 7:12
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