The HLA ligandome landscape of chronic myeloid leukemia delineates novel T-cell epitopes for immunotherapy.
Blood
; 133(6): 550-565, 2019 02 07.
Article
in En
| MEDLINE
| ID: mdl-30530751
ABSTRACT
Antileukemia immunity plays an important role in disease control and maintenance of tyrosine kinase inhibitor (TKI)-free remission in chronic myeloid leukemia (CML). Thus, antigen-specific immunotherapy holds promise for strengthening immune control in CML but requires the identification of CML-associated targets. In this study, we used a mass spectrometry-based approach to identify naturally presented HLA class I- and class II-restricted peptides in primary CML samples. Comparative HLA ligandome profiling using a comprehensive dataset of different hematological benign specimens and samples from CML patients in deep molecular remission delineated a panel of novel frequently presented CML-exclusive peptides. These nonmutated target antigens are of particular relevance because our extensive data-mining approach suggests the absence of naturally presented BCR-ABL- and ABL-BCR-derived HLA-restricted peptides and the lack of frequent tumor-exclusive presentation of known cancer/testis and leukemia-associated antigens. Functional characterization revealed spontaneous T-cell responses against the newly identified CML-associated peptides in CML patient samples and their ability to induce multifunctional and cytotoxic antigen-specific T cells de novo in samples from healthy volunteers and CML patients. Thus, these antigens are prime candidates for T-cell-based immunotherapeutic approaches that may prolong TKI-free survival and even mediate cure of CML patients.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
T-Lymphocytes, Cytotoxic
/
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
/
CD4-Positive T-Lymphocytes
/
Fusion Proteins, bcr-abl
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Epitopes, T-Lymphocyte
/
HLA Antigens
/
Antigens, Neoplasm
Limits:
Humans
Language:
En
Journal:
Blood
Year:
2019
Document type:
Article
Affiliation country:
Germany