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Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Andersen, MH; Reker, S; Becker, JC; Straten, PT.
The melanoma inhibitor of apoptosis protein: A target for spontaneous cytotoxic T cell responses
J INVEST DERMATOL. 2004; 122(2): 392-399.
Doi: 10.1046/j.0022-202X.2004.22242.x
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- Co-authors Med Uni Graz
- Becker Jürgen Christian
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- Abstract:
- The identification of tumor antigens which expression is essential for the survival of tumor cells is a new avenue to prevent antigen loss variants emerging due to immunoselection, particularly during immune therapy. The melanoma inhibitor of apoptosis protein, ML-IAP (also named livin) counteracts apoptosis induced by death receptors, hypooxgenic conditions, or chemotherapeutic agents. Thus, elevated expression of ML-IAP renders melanoma cells resistant to apoptotic stimuli and thereby potentially contributes to the oncogenic phenotype. Here, we demonstrate that T cells in a large proportion of melanoma patients infiltrating the tumor or circulating in the peripheral blood specifically recognize ML-IAP-derived peptides. Interestingly, the responses against the peptide epitope ML-IAP(280-289) were not restricted to melanoma patients but present among peripheral blood T cells in a few healthy controls. In situ peptide/HLA-A2 multimer staining, however, confirmed the infiltration of ML-IAP-reactive cells into the tumor microenvironment. Moreover, ML-IAP-reactive T cells isolated by magnetic beads coated with peptide/HLA-A2 complexes were cytotoxic against HLA-matched melanoma cells. In conclusion, out data strongly indicate ML-IAP as a suitable target for immunologic intervention.
- Find related publications in this database (Keywords)
- antigens
- cytotoxic T lymphocytes
- epitopes
- human
- peptides
- tumor immunity