Immunogenicity of HLA-A1-restricted peptides derived from S100A4 (metastasin 1) in melanoma patients
Research output: Contribution to journal › Journal article › Research › peer-review
S100A4 (metastasin 1) belongs to the S100 family of Ca(2+) binding proteins. While not present in most differentiated adult tissues, S100A4 is upregulated in the micromilieu of tumors. It is primarily expressed by tumor-associated macrophages, fibroblasts, and tumor endothelial cells. Due to its strong induction in tumors S100A4 is a promising target for cancer immunotherapy. By reverse immunology, using epitope prediction programs, we identified 3 HLA-A1-restricted peptide epitopes (S100A4 A1-1, A1-2, and A1-3) which are subject to human T cell responses as detected in peripheral blood of melanoma patients by means of IFN-gamma ELISPOT and cytotoxicity assays. In addition, IFN-gamma responses to S100A4 A1-2 can not only be induced by stimulation of T cells with peptide-loaded DC but also by stimulation with S100A4 protein-loaded DC, indicating that this epitope is indeed generated by processing of the endogenously expressed protein. In addition, S100A4 A1-2 reactive T cells demonstrate lysis of HLA-A1(+) fibroblasts in comparison to HLA-A1(-) fibroblasts. In summary, this HLA-A1-restricted peptide epitope is a candidate for immunotherapeutical approaches targeting S100A4-expressing cells in the tumor stroma.
Original language | English |
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Journal | Cancer Immunology, Immunotherapy |
Volume | 58 |
Issue number | 8 |
Pages (from-to) | 1265-73 |
Number of pages | 9 |
ISSN | 0340-7004 |
DOIs | |
Publication status | Published - 2009 |
Bibliographical note
Keywords: Amino Acid Sequence; Cell Line, Tumor; Cells, Cultured; Epitopes; HLA-A1 Antigen; Humans; Interferon-gamma; Melanoma; Molecular Sequence Data; Peptide Fragments; S100 Proteins; Sequence Alignment; Skin Neoplasms; T-Lymphocytes, Cytotoxic
ID: 20568632