A meta-analysis of HLA peptidome composition in different hematological entities: entity-specific dividing lines and "pan-leukemia" antigens.
Hematological malignancies (HM) are highly amenable targets for immunotherapeutic intervention and may be effectively treated by antigen-specific T-cell based treatment. Recent studies demonstrate that physiologically occurring anti-cancer T-cell responses in certain HM entities target broadly presented non-mutated epitopes. HLA ligands are thus implied as prime targets for broadly applicable and antigen-specific off-the-shelf compounds. With the aim of assessing the presence of common targets shared among different HM which may enable addressing a larger patient collective we conducted a meta-analysis of 83 mass spectrometry-based HLA peptidome datasets (comprising 40,361 unique peptide identifications) across four major HM (19 AML, 16 CML, 35 CLL, and 13 MM/MCL samples) and investigated similarities and differences within the HLA presented antigenic landscape. We found the cancer HLA peptidome datasets to cluster specifically along entity and lineage lines, suggesting that the immunopeptidome directly reflects the differences in the underlying (tumor-)biology. In line with these findings, we only detected a small set of entity-spanning antigens, which were predominantly characterized by low presentation frequencies within the different patient cohorts. These findings suggest that design of T-cell immunotherapies for the treatment of HM should ideally be conducted in an entity-specific fashion.
Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.|Applied Bioinformatics, Center for Bioinformatics and Department of Computer Science, University of Tübingen, Tübingen, Germany.
Linus
L
Backert
Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.|Immatics Biotechnologies GmbH, Tübingen, Germany.
Daniel Johannes
DJ
Kowalewski
Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.|Department of Hematology and Oncology, University of Tübingen, Tübingen, Germany.
Simon
S
Walz
Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.|Immatics Biotechnologies GmbH, Tübingen, Germany.
Heiko
H
Schuster
Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.|Department of Hematology and Oncology, University of Tübingen, Tübingen, Germany.
Claudia
C
Berlin
Department of Neurosurgery, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Marian Christoph
MC
Neidert
Department of Hematology, Oncology, Hemostaseology and SCT, University Hospital RWTH Aachen, Aachen, Germany.
Mirle
M
Schemionek
Department of Hematology, Oncology, Hemostaseology and SCT, University Hospital RWTH Aachen, Aachen, Germany.
Tim H
TH
Brümmendorf
University Hospital Leipzig, Department of Hematology and Oncology, Leipzig, Germany.
Vladan
V
Vucinic
University Hospital Leipzig, Department of Hematology and Oncology, Leipzig, Germany.
Dietger
D
Niederwieser
Department of Hematology and Oncology, University of Tübingen, Tübingen, Germany.
Lothar
L
Kanz
Department of Hematology and Oncology, University of Tübingen, Tübingen, Germany.|Clinical Cooperation Unit Translational Immunology, German Cancer Consortium (DKTK), DKFZ Partner Site Tübingen, Tübingen, Germany.
Helmut Rainer
HR
Salih
Applied Bioinformatics, Center for Bioinformatics and Department of Computer Science, University of Tübingen, Tübingen, Germany.|Quantitative Biology Center, University of Tübingen, Tübingen, Germany.|Biomolecular Interactions, Max Planck Institute for Developmental Biology, Tübingen, Germany.
Oliver
O
Kohlbacher
Department of Hematology and Oncology, University of Tübingen, Tübingen, Germany.
Katja
K
Weisel
Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.|German Cancer Consortium (DKTK), DKFZ Partner Site Tübingen, Tübingen, Germany.
Hans-Georg
HG
Rammensee
Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.|German Cancer Consortium (DKTK), DKFZ Partner Site Tübingen, Tübingen, Germany.
Stefan
S
Stevanovic
Department of Hematology and Oncology, University of Tübingen, Tübingen, Germany.
Juliane Sarah
JS
Walz
D000951:Antigens, Neoplasm / Q000276:immunology; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D018604:Epitope Mapping / Q000379:methods; D000939:Epitopes / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D006680:HLA Antigens / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D019337:Hematologic Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D006801:Humans; D007167:Immunotherapy; D007938:Leukemia / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D008024:Ligands; D010455:Peptides / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism
D000951:Antigens, Neoplasm; D000939:Epitopes; D006680:HLA Antigens; D008024:Ligands; D010455:Peptides
HLA; cancer immunotherapy; hematological malignancies; mass spectrometry; tumor antigen