TY  - JOUR
AU  - Borchers, S.
AU  - Maβlo, C.
AU  - Müller, C. A.
AU  - Tahedl, A.
AU  - Volkind, J.
AU  - Nowak, Y.
AU  - Umansky, V.
AU  - Esterlechner, J.
AU  - Frank, M. H.
AU  - Ganss, C.
AU  - Kluth, M. A.
AU  - Utikal, Jochen
TI  - Detection of ABCB5 tumour antigen-specific CD8+ T cells in melanoma patients and implications for immunotherapy.
JO  - Clinical and experimental immunology
VL  - 191
IS  - 1
SN  - 0009-9104
CY  - Oxford
PB  - Wiley-Blackwell52004
M1  - DKFZ-2019-00080
SP  - 74 - 83
PY  - 2018
AB  - 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.
KW  - ABCB5 protein, human (NLM Chemicals)
KW  - ATP Binding Cassette Transporter, Subfamily B, Member 1 (NLM Chemicals)
KW  - Antigens, Neoplasm (NLM Chemicals)
KW  - Cytokines (NLM Chemicals)
KW  - Epitopes, T-Lymphocyte (NLM Chemicals)
KW  - Peptides (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:28940439
C2  - pmc:PMC5721238
DO  - DOI:10.1111/cei.13053
UR  - https://inrepo02.dkfz.de/record/142297
ER  -