Natural CD8+ T-cell responses against MHC class I epitopes of the HER-2/ neu oncoprotein in patients with epithelial tumors.
|Title:||Natural CD8+ T-cell responses against MHC class I epitopes of the HER-2/ neu oncoprotein in patients with epithelial tumors.|
|Source:||Cancer immunology and immunotherapy, 52 (12|
|Added Details:||Sotiropoulou, Panagiota
Tsavaris, Nick B
Baxevanis, Constantin N
|Document Type:||Electronic Resource|
|Abstract:||HER-2/ neu is an immunogenic protein eliciting both humoral and cellular immune responses in patients with HER-2/ neu-positive ((+)) tumors. Preexisting cytotoxic T lymphocyte (CTL) immunity to HER-2/ neu has so far been mainly evaluated in terms of detection of CTL precursor (CTLp) frequencies to the immunogenic HLA-A2-binding nona-peptide 369-377 (HER-2(9(369))). In the present study, we examined patients with HER-2/ neu(+) breast, ovarian, lung, colorectal, and prostate cancers for preexisting CTL immunity to four recently described HER-2/ neu-derived and HLA-A2-restricted "cytotoxic" peptides and to a novel one spanning amino acids 777-785 also with HLA-A2-binding motif. We utilized enzyme-linked immunosorbent spot (ELISpot) assay, which allows a quantitative and functional assessment of T cells directed against specific peptides after only brief in vitro incubation. CTL reactivity was determined with an interferon gamma (IFN-gamma) ELISpot assay detecting T cells at the single cell level secreting IFN-gamma. CTLp were defined as peptide-specific precursors per 10(6) peripheral blood mononuclear cells (PBMCs). Patients' PBMCs with increased CTLp were also tested against autologous tumor targets and peptide-pulsed dendritic cells (DCs) in cytotoxicity assays. We also studied patients with HER-2/ neu-negative ((-)) tumors and healthy individuals. Of the HER-2/neu(+) patients examined, 31% had increased CTLp to HER-2(9(952)), 19% to HER-2(9(665)), 16% to HER-2(9(689)), and 12.5% HER-2(9(435)), whereas only 2 of 32 patients (6%) responded to HER-2(9(777)). The CTLp recognizing HER-2(9(952)) were extremely high in two patients with breast cancer, one with lung cancer, and one with prostate cancer. None of the HER-2/neu(-) patients or healthy donors exhibited increased CTLp to any of these peptides. Besides IFN-gamma production, preexisting CTL immunity to all five HER-2/ neu peptides was also shown in cytotoxicity assays where patients' PBMCs with increased CTLp spec
|Index Terms:||Sciences bio-médicales et agricoles, Adult, Aged, CD8-Positive T-Lymphocytes -- immunology, Cell Division, Dendritic Cells -- immunology, Enzyme-Linked Immunosorbent Assay, Epitopes -- immunology, Female, HLA-A2 Antigen -- immunology, Humans, Immunization, Immunophenotyping, Interferon-gamma -- biosynthesis, Leukocytes, Mononuclear -- cytology -- drug effects -- immunology, Male, Middle Aged, Neoplasms -- immunology, Peptide Fragments -- immunology -- metabolism, Receptor, erbB-2 -- immunology, T-Lymphocytes, Cytotoxic -- immunology, info:eu-repo/semantics/article, info:ulb-repo/semantics/articlePeerReview, info:ulb-repo/semantics/openurl/article|
|Availability:||Open access content. Open access content|
|Note:||No full-text files
|Other Numbers:||EQY oai:dipot.ulb.ac.be:2013/142124
|Contributing Source:||UNIVERSITE LIBRE DE BRUXELLES
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