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000142297 1001_ $$00000-0003-3514-7523$$aBorchers, S.$$b0
000142297 245__ $$aDetection of ABCB5 tumour antigen-specific CD8+ T cells in melanoma patients and implications for immunotherapy.
000142297 260__ $$aOxford$$bWiley-Blackwell52004$$c2018
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000142297 520__ $$aATP 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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000142297 650_7 $$2NLM Chemicals$$aABCB5 protein, human
000142297 650_7 $$2NLM Chemicals$$aATP Binding Cassette Transporter, Subfamily B, Member 1
000142297 650_7 $$2NLM Chemicals$$aAntigens, Neoplasm
000142297 650_7 $$2NLM Chemicals$$aCytokines
000142297 650_7 $$2NLM Chemicals$$aEpitopes, T-Lymphocyte
000142297 650_7 $$2NLM Chemicals$$aPeptides
000142297 7001_ $$aMaβlo, C.$$b1
000142297 7001_ $$aMüller, C. A.$$b2
000142297 7001_ $$aTahedl, A.$$b3
000142297 7001_ $$aVolkind, J.$$b4
000142297 7001_ $$0P:(DE-He78)a901a40b998327632773e7c6da807c0b$$aNowak, Y.$$b5$$udkfz
000142297 7001_ $$0P:(DE-He78)38be34240daf8b47325afc7910e77f7b$$aUmansky, V.$$b6$$udkfz
000142297 7001_ $$aEsterlechner, J.$$b7
000142297 7001_ $$aFrank, M. H.$$b8
000142297 7001_ $$aGanss, C.$$b9
000142297 7001_ $$aKluth, M. A.$$b10
000142297 7001_ $$0P:(DE-He78)a229f7724466e7efadf4a1ace1ff8af3$$aUtikal, Jochen$$b11$$eLast author$$udkfz
000142297 773__ $$0PERI:(DE-600)218531-3$$a10.1111/cei.13053$$gVol. 191, no. 1, p. 74 - 83$$n1$$p74 - 83$$tClinical and experimental immunology$$v191$$x0009-9104$$y2018
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