Home > Publications database > Detection of ABCB5 tumour antigen-specific CD8+ T cells in melanoma patients and implications for immunotherapy. > print

001     142297
005     20240229105147.0
024 7 _ |2 doi
|a 10.1111/cei.13053
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024 7 _ |2 ISSN
|a 0964-2536
024 7 _ |2 ISSN
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037 _ _ |a DKFZ-2019-00080
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082 _ _ |a 570
100 1 _ |0 0000-0003-3514-7523
|a Borchers, S.
|b 0
245 _ _ |a Detection of ABCB5 tumour antigen-specific CD8+ T cells in melanoma patients and implications for immunotherapy.
260 _ _ |a Oxford
|b Wiley-Blackwell52004
|c 2018
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|a Journal Article
520 _ _ |a 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.
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650 _ 7 |2 NLM Chemicals
|a ABCB5 protein, human
650 _ 7 |2 NLM Chemicals
|a ATP Binding Cassette Transporter, Subfamily B, Member 1
650 _ 7 |2 NLM Chemicals
|a Antigens, Neoplasm
650 _ 7 |2 NLM Chemicals
|a Cytokines
650 _ 7 |2 NLM Chemicals
|a Epitopes, T-Lymphocyte
650 _ 7 |2 NLM Chemicals
|a Peptides
700 1 _ |a Maβlo, C.
|b 1
700 1 _ |a Müller, C. A.
|b 2
700 1 _ |a Tahedl, A.
|b 3
700 1 _ |a Volkind, J.
|b 4
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|a Nowak, Y.
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|a Umansky, V.
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700 1 _ |a Esterlechner, J.
|b 7
700 1 _ |a Frank, M. H.
|b 8
700 1 _ |a Ganss, C.
|b 9
700 1 _ |a Kluth, M. A.
|b 10
700 1 _ |0 P:(DE-He78)a229f7724466e7efadf4a1ace1ff8af3
|a Utikal, Jochen
|b 11
|e Last author
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773 _ _ |0 PERI:(DE-600)218531-3
|a 10.1111/cei.13053
|g Vol. 191, no. 1, p. 74 - 83
|n 1
|p 74 - 83
|t Clinical and experimental immunology
|v 191
|x 0009-9104
|y 2018
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