| Title: |
HLA Ligand Atlas: a benign reference of HLA-presented peptides to improve T-cell-based cancer immunotherapy |
| Authors: |
Marcu, Ana; Bichmann, Leon; Kuchenbecker, Leon; Kowalewski, Daniel Johannes; Freudenmann, Lena Katharina; Backert, Linus; Mühlenbruch, Lena; Szolek, András; Lübke, Maren; Wagner, Philipp; Engler, Tobias; Matovina, Sabine; Wang, Jian; Hauri-Hohl, Mathias; Martin, Roland; Kapolou, Konstantina; Walz, Juliane Sarah; Velz, Julia; Moch, Holger; Regli, Luca; Silginer, Manuela; Weller, Michael; Löffler, Markus W; Erhard, Florian; Schlosser, Andreas; Kohlbacher, Oliver; Stevanović, Stefan; Rammensee, Hans-Georg; Neidert, Marian Christoph |
| Source: |
Marcu, Ana; Bichmann, Leon; Kuchenbecker, Leon; Kowalewski, Daniel Johannes; Freudenmann, Lena Katharina; Backert, Linus; Mühlenbruch, Lena; Szolek, András; Lübke, Maren; Wagner, Philipp; Engler, Tobias; Matovina, Sabine; Wang, Jian; Hauri-Hohl, Mathias; Martin, Roland; Kapolou, Konstantina; Walz, Juliane Sarah; Velz, Julia; Moch, Holger; Regli, Luca; Silginer, Manuela; Weller, Michael; Löffler, Markus W; Erhard, Florian; Schlosser, Andreas; Kohlbacher, Oliver; Stevanović, Stefan; Rammensee, Hans-Georg; Neidert, Marian Christoph (2021). HLA Ligand Atlas: a benign reference of HLA-presented peptides to improve T-cell-based cancer immunotherapy. Journal for ImmunoTherapy of Cancer, 9(4):18. |
| Publisher Information: |
BioMed Central |
| Publication Year: |
2021 |
| Collection: |
University of Zurich (UZH): ZORA (Zurich Open Repository and Archive |
| Subject Terms: |
Clinic for Neurology; Institute of Pathology and Molecular Pathology; Clinic for Neurosurgery; Medical Clinic; Clinic for Surgery; 610 Medicine & health |
| Description: |
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 ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
2051-1426 |
| Relation: |
https://www.zora.uzh.ch/id/eprint/203647/1/Marcu_JTC_2021.pdf; info:pmid/33858848; urn:issn:2051-1426 |
| Availability: |
https://www.zora.uzh.ch/id/eprint/203647/; https://www.zora.uzh.ch/id/eprint/203647/1/Marcu_JTC_2021.pdf |
| Rights: |
info:eu-repo/semantics/openAccess ; Creative Commons: Attribution 4.0 International (CC BY 4.0) ; http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.907D4541 |
| Database: |
BASE |