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

Details

Serval ID
serval:BIB_848F6AADEDBE
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
CIITA-Transduced Glioblastoma Cells Uncover a Rich Repertoire of Clinically Relevant Tumor-Associated HLA-II Antigens.
Journal
Molecular & cellular proteomics
Author(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
Publication state
Published
Issued date
06/01/2021
Peer-reviewed
Oui
Volume
20
Pages
100032
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Abstract
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.
Keywords
Analytical Chemistry, Biochemistry, Molecular Biology, Antigen discovery, Class II major histocompatibility complex transactivator, Glioblastoma, Immunopeptidomics
Pubmed
Web of science
Open Access
Yes
Funding(s)
European Research Council (ERC)
Create date
09/10/2020 7:59
Last modification date
05/06/2021 5:33
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