HLA Ligand Atlas: a benign reference of HLA-presented peptides to improve T-cell-based cancer immunotherapy
| Autor: | Mathias Hauri-Hohl, Konstantina Kapolou, Philipp Wagner, Holger Moch, Lena Mühlenbruch, Linus Backert, Ana Marcu, Leon Kuchenbecker, Maren Lübke, Florian Erhard, Marian Christoph Neidert, Leon Bichmann, András Szolek, Luca Regli, Julia Velz, T Engler, Michael Weller, Jian Wang, Andreas Schlosser, Hans-Georg Rammensee, Juliane S. Walz, Markus W. Löffler, Sabine Matovina, Lena Katharina Freudenmann, Roland Martin, Manuela Silginer, Daniel J. Kowalewski, Oliver Kohlbacher, Stefan Stevanovic |
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| Přispěvatelé: | University of Zurich, Marcu, Ana |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Male Proteomics Cancer Research Proteome medicine.medical_treatment T-Lymphocytes Ligands Immunotherapy Adoptive 0302 clinical medicine Cancer immunotherapy antigens HLA Antigens Tandem Mass Spectrometry Neoplasms Immunology and Allergy tumor-associated 1306 Cancer Research Databases Protein RC254-282 Aged 80 and over Receptors Chimeric Antigen Neoplasms. Tumors. Oncology. Including cancer and carcinogens adaptive immunity Middle Aged medicine.anatomical_structure 3004 Pharmacology Oncology 030220 oncology & carcinogenesis translational medical research 2723 Immunology and Allergy Molecular Medicine 2730 Oncology Female immunotherapy T cell Immunology Antigen presentation 610 Medicine & health Human leukocyte antigen Biology 03 medical and health sciences 10180 Clinic for Neurosurgery Immune system Antigen Antigens Neoplasm 10049 Institute of Pathology and Molecular Pathology medicine Humans 10220 Clinic for Surgery Aged Pharmacology 2403 Immunology Infant Newborn Infant Basic Tumor Immunology Immunotherapy 10040 Clinic for Neurology Transplantation antigen presentation 030104 developmental biology 10036 Medical Clinic carbohydrate 1313 Molecular Medicine Cancer research Peptides Chromatography Liquid |
| Zdroj: | Journal for Immunotherapy of Cancer Journal for ImmunoTherapy of Cancer, Vol 9, Iss 4 (2021) Journal for ImmunoTherapy of Cancer, 9 (4) |
| ISSN: | 2051-1426 |
| Popis: | Background The human leucocyte antigen (HLA) complex controls adaptive immunity by presenting defined fractions of the intracellular and extracellular protein content to immune cells. Understanding the benign HLA ligand repertoire is a prerequisite to define safe T-cell-based immunotherapies against cancer. Due to the poor availability of benign tissues, if available, normal tissue adjacent to the tumor has been used as a benign surrogate when defining tumor-associated antigens. However, this comparison has proven to be insufficient and even resulted in lethal outcomes. In order to match the tumor immunopeptidome with an equivalent counterpart, we created the HLA Ligand Atlas, the first extensive collection of paired HLA-I and HLA-II immunopeptidomes from 227 benign human tissue samples. This dataset facilitates a balanced comparison between tumor and benign tissues on HLA ligand level. Methods Human tissue samples were obtained from 16 subjects at autopsy, five thymus samples and two ovary samples originating from living donors. HLA ligands were isolated via immunoaffinity purification and analyzed in over 1200 liquid chromatography mass spectrometry runs. Experimentally and computationally reproducible protocols were employed for data acquisition and processing. Results The initial release covers 51 HLA-I and 86 HLA-II allotypes presenting 90,428 HLA-I- and 142,625 HLA-II ligands. The HLA allotypes are representative for the world population. We observe that immunopeptidomes differ considerably between tissues and individuals on source protein and HLA-ligand level. Moreover, we discover 1407 HLA-I ligands from non-canonical genomic regions. Such peptides were previously described in tumors, peripheral blood mononuclear cells (PBMCs), healthy lung tissues and cell lines. In a case study in glioblastoma, we show that potential on-target off-tumor adverse events in immunotherapy can be avoided by comparing tumor immunopeptidomes to the provided multi-tissue reference. Conclusion Given that T-cell-based immunotherapies, such as CAR-T cells, affinity-enhanced T cell transfer, cancer vaccines and immune checkpoint inhibition, have significant side effects, the HLA Ligand Atlas is the first step toward defining tumor-associated targets with an improved safety profile. The resource provides insights into basic and applied immune-associated questions in the context of cancer immunotherapy, infection, transplantation, allergy and autoimmunity. It is publicly available and can be browsed in an easy-to-use web interface at https://hla-ligand-atlas.org . Journal for ImmunoTherapy of Cancer, 9 (4) ISSN:2051-1426 |
| Databáze: | OpenAIRE |
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