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@ARTICLE{Borchers:142297,
author = {S. Borchers and C. Maβlo and C. A. Müller and A. Tahedl
and J. Volkind and Y. Nowak$^*$ and V. Umansky$^*$ and J.
Esterlechner and M. H. Frank and C. Ganss and M. A. Kluth
and J. Utikal$^*$},
title = {{D}etection of {ABCB}5 tumour antigen-specific {CD}8+ {T}
cells in melanoma patients and implications for
immunotherapy.},
journal = {Clinical and experimental immunology},
volume = {191},
number = {1},
issn = {0009-9104},
address = {Oxford},
publisher = {Wiley-Blackwell52004},
reportid = {DKFZ-2019-00080},
pages = {74 - 83},
year = {2018},
abstract = {ATP binding cassette subfamily B member 5 (ABCB5) has been
identified as a tumour-initiating cell marker and is
expressed in various malignancies, including melanoma.
Moreover, treatment with anti-ABCB5 monoclonal antibodies
has been shown to inhibit tumour growth in
xenotransplantation models. Therefore, ABCB5 represents a
potential target for cancer immunotherapy. However, cellular
immune responses against ABCB5 in humans have not been
described so far. Here, we investigated whether
ABCB5-reactive T cells are present in human melanoma
patients and tested the applicability of ABCB5-derived
peptides for experimental induction of human T cell
responses. Peripheral blood mononuclear cells (PBMNC)
isolated from blood samples of melanoma patients
(n = 40) were stimulated with ABCB5 peptides, followed
by intracellular cytokine staining (ICS) for interferon
(IFN)-γ and tumour necrosis factor (TNF)-α. To evaluate
immunogenicity of ABCB5 peptides in naive healthy donors,
CD8 T cells were co-cultured with ABCB5 antigen-loaded
autologous dendritic cells (DC). ABCB5 reactivity in
expanded T cells was assessed similarly by ICS.
ABCB5-reactive CD8+ T cells were detected ex vivo in 19 of
29 patients, melanoma antigen recognised by T cells
(MART-1)-reactive CD8+ T cells in six of 21 patients. In
this small, heterogeneous cohort, reactivity against ABCB5
was significantly higher than against MART-1. It occurred
significantly more often and independently of clinical
characteristics. Reactivity against ABCB5 could be induced
in 14 of 16 healthy donors in vitro by repeated stimulation
with peptide-loaded autologous DC. As ABCB5-reactive CD8 T
cells can be found in the peripheral blood of melanoma
patients and an ABCB5-specific response can be induced in
vitro in naive donors, ABCB5 could be a new target for
immunotherapies in melanoma.},
keywords = {ABCB5 protein, human (NLM Chemicals) / ATP Binding Cassette
Transporter, Subfamily B, Member 1 (NLM Chemicals) /
Antigens, Neoplasm (NLM Chemicals) / Cytokines (NLM
Chemicals) / Epitopes, T-Lymphocyte (NLM Chemicals) /
Peptides (NLM Chemicals)},
cin = {G300},
ddc = {570},
cid = {I:(DE-He78)G300-20160331},
pnm = {317 - Translational cancer research (POF3-317)},
pid = {G:(DE-HGF)POF3-317},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:28940439},
pmc = {pmc:PMC5721238},
doi = {10.1111/cei.13053},
url = {https://inrepo02.dkfz.de/record/142297},
}