A meta-analysis of HLA peptidome composition in different hematological entities: entity-specific dividing lines and "pan-leukemia" antigens
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A meta-analysis of HLA peptidome composition in different hematological entities: entity-specific dividing lines and "pan-leukemia" antigens : entity-specific dividing lines and "pan-leukemia" antigens. / Backert, Linus; Kowalewski, Daniel Johannes; Walz, Simon; Schuster, Heiko; Berlin, Claudia; Neidert, Marian Christoph; Schemionek, Mirle; Brümmendorf, Tim H; Vucinic, Vladan; Niederwieser, Dietger; Kanz, Lothar; Salih, Helmut Rainer; Kohlbacher, Oliver; Weisel, Katja; Rammensee, Hans-Georg; Stevanovic, Stefan; Walz, Juliane Sarah.
In: ONCOTARGET, Vol. 8, No. 27, 04.07.2017, p. 43915-43924.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - A meta-analysis of HLA peptidome composition in different hematological entities: entity-specific dividing lines and "pan-leukemia" antigens
T2 - entity-specific dividing lines and "pan-leukemia" antigens
AU - Backert, Linus
AU - Kowalewski, Daniel Johannes
AU - Walz, Simon
AU - Schuster, Heiko
AU - Berlin, Claudia
AU - Neidert, Marian Christoph
AU - Schemionek, Mirle
AU - Brümmendorf, Tim H
AU - Vucinic, Vladan
AU - Niederwieser, Dietger
AU - Kanz, Lothar
AU - Salih, Helmut Rainer
AU - Kohlbacher, Oliver
AU - Weisel, Katja
AU - Rammensee, Hans-Georg
AU - Stevanovic, Stefan
AU - Walz, Juliane Sarah
PY - 2017/7/4
Y1 - 2017/7/4
N2 - 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.
AB - 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.
KW - Antigens, Neoplasm
KW - Cell Line, Tumor
KW - Cluster Analysis
KW - Epitope Mapping
KW - Epitopes
KW - HLA Antigens
KW - Hematologic Neoplasms
KW - Humans
KW - Immunotherapy
KW - Leukemia
KW - Ligands
KW - Peptides
KW - Journal Article
U2 - 10.18632/oncotarget.14918
DO - 10.18632/oncotarget.14918
M3 - SCORING: Journal article
C2 - 28159928
VL - 8
SP - 43915
EP - 43924
JO - ONCOTARGET
JF - ONCOTARGET
SN - 1949-2553
IS - 27
ER -