| Reference |
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| Reference Type | Literature | IEDB_Reference:1039604 |
| Title | CIITA-Transduced Glioblastoma Cells Uncover a Rich Repertoire of Clinically Relevant Tumor-Associated HLA-II Antigens. | |
| Authors | Greta Forlani; Justine Michaux; HuiSong Pak; Florian Huber; Elodie Lauret Marie Joseph; Elise Ramia; Brian J Stevenson; Michael Linnebacher; Roberto S Accolla; Michal Bassani-Sternberg | |
| Affiliations | Laboratories of General Pathology and Immunology "Giovanna Tosi", Department of Medicine and Surgery, School of Medicine, University of Insubria, Varese, Italy; Ludwig Cancer Research Center, University of Lausanne, Lausanne, Switzerland; Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland; SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland; Department of General Surgery, Molecular Oncology and Immunotherapy, University Medical Center Rostock, Rostock, Germany; Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland. Electronic address: Michal.bassani@chuv.ch. | |
| Journal | Mol Cell Proteomics | |
| Year | 2021 | |
| 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. | |
| Curation Last Updated | 2025-03-04 22:38:05 | |