TY - JOUR
T1 - Immunogenicity of HLA-A1-restricted peptides derived from S100A4 (metastasin 1) in melanoma patients
AU - Hofmeister-Mueller, Valeska
AU - Vetter-Kauczok, Claudia S
AU - Ullrich, Ramona
AU - Meder, Katharina
AU - Lukanidin, Eugene
AU - Broecker, Eva-Bettina
AU - Straten, Per thor
AU - Andersen, Mads Hald
AU - Schrama, David
AU - Becker, Juergen C
N1 - 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
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
U2 - 10.1007/s00262-008-0640-0
DO - 10.1007/s00262-008-0640-0
M3 - Journal article
C2 - 19139886
SN - 0340-7004
VL - 58
SP - 1265
EP - 1273
JO - Cancer Immunology, Immunotherapy
JF - Cancer Immunology, Immunotherapy
IS - 8
ER -
