Detection of ABCB5 tumour antigen‐specific CD8+ T cells in melanoma patients and implications for immunotherapy
ATP binding cassette subfamily B member 5 (ABCB5) has been identified asa tumour-initiating cell marker and is expressed in various malignancies,including melanoma. Moreover, treatment with anti-ABCB5 monoclonalantibodies has been shown to inhibit tumour growth in xenotransplantationmodels. Therefo...
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| Main Authors: | , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2018
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| In: |
Clinical & experimental immunology
Year: 2017, Volume: 191, Issue: 1, Pages: 74-83 |
| ISSN: | 1365-2249 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1111/cei.13053
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| Author Notes: | S. Borchers, C. Maβlo, C.A. Müller, A. Tahedl, J. Volkind, Y. Nowak, V. Umansky, J. Esterlechner, M.H. Frank, C. Ganss, M.A. Kluth and J. Utikal |
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| 246 | 3 | 3 | |a Detection of ABCB 5 tumour antigen‐specific CD8 + T cells in melanoma patients and implications for immunotherapy |
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| 520 | |a ATP binding cassette subfamily B member 5 (ABCB5) has been identified asa tumour-initiating cell marker and is expressed in various malignancies,including melanoma. Moreover, treatment with anti-ABCB5 monoclonalantibodies has been shown to inhibit tumour growth in xenotransplantationmodels. Therefore, ABCB5 represents a potential target for cancerimmunotherapy. However, cellular immune responses against ABCB5 inhumans have not been described so far. Here, we investigated whetherABCB5-reactive T cells are present in human melanoma patients and testedthe applicability of ABCB5-derived peptides for experimental induction ofhuman T cell responses. Peripheral blood mononuclear cells (PBMNC)isolated from blood samples of melanoma patients (n540) were stimulatedwith ABCB5 peptides, followed by intracellular cytokine staining (ICS) forinterferon (IFN)-gand tumour necrosis factor (TNF)-a. To evaluateimmunogenicity of ABCB5 peptides in naive healthy donors, CD8 T cellswere co-cultured with ABCB5 antigen-loaded autologous dendritic cells(DC). ABCB5 reactivity in expanded T cells was assessed similarly by ICS.ABCB5-reactive CD81T cells were detectedex vivoin 19 of 29 patients,melanoma antigen recognised by T cells (MART-1)-reactive CD81T cells insix of 21 patients. In this small, heterogeneous cohort, reactivity againstABCB5 was significantly higher than against MART-1. It occurredsignificantly more often and independently of clinical characteristics.Reactivity against ABCB5 could be induced in 14 of 16 healthy donorsinvitroby repeated stimulation with peptide-loaded autologous DC. AsABCB5-reactive CD8 T cells can be found in the peripheral blood ofmelanoma patients and an ABCB5-specific response can be inducedin vitroin naive donors, ABCB5 could be a new target for immunotherapies inmelanoma. | ||
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