Hi-TIDe : Immunopeptidomics

Our main goal is to identify clinically relevant cancer specific Human Leukocyte Antigen (HLA) ligands that will guide the development of personalized cancer immunotherapy using mass-spectrometry (MS), currently the only methodology to unbiasedly identify HLA binding peptides that are presented in vivo to cytotoxic T cells.

Proteogenomics and MS-based immunopeptidomics approaches to identify HLA ligands derived from tumor-associated proteins, mutated neoantigens, non-canonical ORFs and post translationally modified peptides.

• We developed a high-throughput and in depth MS-based immunopeptidomics pipeline that now enables robust and reproducible sample preparation and measurement of HLA/MHC class I and class II peptides. We are currently applying this methodology to identify tumor-associated ligands extracted from cell lines and tumor tissues from humans and nice models. 
• We have initiated fundamental discovery work to elucidate how tumor cells present antigens and what are the bases of tumor immunogenicity.
• We are investigating the differences between tumor types in terms of antigen presentation and how drugs modulate the immunopeptidome.
• In collaboration with the Vital-IT group (SIB), we have established a continuous bio-informatics pipeline enabling direct identification of neoantigens by combining genomic information derived from exome-seq analysis with measured immunopeptidomics data.
• In collaboration with Pr David Gfeller, we are improving the performance of HLA class I and class II binding prediction tools by training them with our measured immunopeptidomics data.
• We apply proteogenomics approaches to identify personalized neo-antigens from patient tumor samples. These tumor-specific antigens will be further developed into personalized cancer vaccines or to enrich tumor-reactive and antigen-specific T cells for adoptive T cell-based therapies.

• Chong C., Müller M., Pak HuiSong, Harnett D., Huber F., Grun D., Leleu M., Auger A., Arnaud M., Stevenson B. J., Michaux J., Bilic I., Hirsekorn A., Calviello L., Simó-Riudalbas L., Planet E., Lubiński J., Bryśkiewicz M., Wiznerowicz M., Xenarios I., Zhang L., Trono D., Harari A., Ohler U., Coukos G., Bassani-Sternberg M*. (2020) Integrated proteogenomic deep sequencing and analytics accurately identify non-canonical peptides in tumor immunopeptidomes. Nature Communications. 11 (1). [10.1038/s41467-020-14968-9] *Corresponding author
• Racle J., Michaux J., Rockinger G.A., Arnaud M., Bobisse S., Chong C., Guillaume P., Coukos G., Harari A., Jandus C., Bassani-Sternberg M*., Gfeller D*. (2019) Robust prediction of HLA class II epitopes by deep motif deconvolution of immunopeptidomes. Nature Biotechnology. 37 (11) pp. 1283-1286. [10.1038/s41587-019-0289-6] *Co-corresponding author
• Bassani-Sternberg M.*, Digklia A., Huber F., Wagner D., Sempoux C., Stevenson B. J., Thierry A.-C., Michaux J., Pak HuiSong, Racle J., Boudousquie C., Balint K., Coukos G., Gfeller D., Martin Lluesma S., Harari A., Demartines N., Kandalaft L. E.* (2019) A Phase Ib Study of the Combination of Personalized Autologous Dendritic Cell Vaccine, Aspirin, and Standard of Care Adjuvant Chemotherapy Followed by Nivolumab for Resected Pancreatic Adenocarcinoma—A Proof of Antigen Discovery Feasibility in Three Patients. Frontiers in Immunology. 10 p. 1832. [10.3389/fimmu.2019.01832][Full text] *Co-corresponding author
• Chong C., Marino F., Pak H., Racle J., Daniel R.T., Müller M., Gfeller D., Coukos G., Bassani-Sternberg M.* (2018) High-throughput and Sensitive Immunopeptidomics Platform Reveals Profound Interferonγ-Mediated Remodeling of the Human Leukocyte Antigen (HLA) Ligandome. Molecular & Cellular Proteomics. 17 (3) pp. 533-548. [10.1074/mcp.TIR117.000383] *Corresponding author
• Bassani-Sternberg M.*, Bräunlein E.*, Klar R., Engleitner T., Sinitcyn P., Audehm S., Straub M., Weber J., Slotta-Huspenina J., Specht K., Martignoni M.E., Werner A., Hein R., H Busch D., Peschel C., Rad R., Cox J., Mann M., Krackhardt A.M. (2016) Direct identification of clinically relevant neoepitopes presented on native human melanoma tissue by mass spectrometry. Nature Communications. 7 p. 13404. [10.1038/ncomms13404] *Co-first author