A meta-analysis of HLA peptidome composition in different hematological entities: entity-specific dividing lines and "pan-leukemia" antigens

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 -