%0 Journal Article
%A Borchers, S.
%A Maβlo, C.
%A Müller, C. A.
%A Tahedl, A.
%A Volkind, J.
%A Nowak, Y.
%A Umansky, V.
%A Esterlechner, J.
%A Frank, M. H.
%A Ganss, C.
%A Kluth, M. A.
%A Utikal, Jochen
%T Detection of ABCB5 tumour antigen-specific CD8+ T cells in melanoma patients and implications for immunotherapy.
%J Clinical and experimental immunology
%V 191
%N 1
%@ 0009-9104
%C Oxford
%I Wiley-Blackwell52004
%M DKFZ-2019-00080
%P 74 - 83
%D 2018
%X 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.
%K ABCB5 protein, human (NLM Chemicals)
%K ATP Binding Cassette Transporter, Subfamily B, Member 1 (NLM Chemicals)
%K Antigens, Neoplasm (NLM Chemicals)
%K Cytokines (NLM Chemicals)
%K Epitopes, T-Lymphocyte (NLM Chemicals)
%K Peptides (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:28940439
%2 pmc:PMC5721238
%R 10.1111/cei.13053
%U https://inrepo02.dkfz.de/record/142297