Level of HER-2/neu protein expression in breast cancer may affect the development of endogenous HER-2/neu-specific immunity
- 1 March 2008
- journal article
- Published by American Association for Cancer Research (AACR) in Molecular Cancer Therapeutics
- Vol. 7 (3), 449-454
- https://doi.org/10.1158/1535-7163.mct-07-0386
Abstract
We questioned whether the incidence or magnitude of the humoral or cellular immune response to the self-tumor antigen HER-2/neu is influenced by the level of HER-2/neu protein overexpression as defined by immunohistochemical staining of tumors in breast cancer patients. We obtained peripheral blood from 104 women with stage II, III, and IV pathologically confirmed HER-2/neu-overexpressing breast cancer. Patients were categorized with +1 (n = 14), +2 (n = 20), or +3 (n = 70) HER-2/neu overexpression by institutional pathologic report. Circulating antibodies to HER-2/neu were evaluated using ELISA. T-cell responses to HER-2/neu were measured using an antigen-specific tritiated thymidine incorporation assay. Eighty-two percent of subjects with HER-2/neu antibodies were +3 overexpressors compared with 18% +2 overexpressors and 0% +1 overexpressors, a highly significant difference (P < 0.001), and there were significant differences in the magnitude of the HER-2/neu-specific antibodies between groups with varying HER-2/neu protein expression (P = 0.022). In addition, 65% of subjects with HER-2/neu-specific T cells were +3 overexpressors compared with 16% +2 overexpressors and 19% +1 overexpressors (P = 0.001). Data presented here indicate that endogenous HER-2/neu-specific humoral and T-cell immunity is greater in patients with +3 protein overexpression in their tumors than in patients with lower levels of HER-2/neu expression. Overexpression of a self-tumor-associated protein is a potential mechanism by which immunogenicity is enhanced and may aid in the identification of biologically relevant proteins to target for immune-based molecular cancer therapies. [Mol Cancer Ther 2008;7(3):449–54]Keywords
This publication has 12 references indexed in Scilit:
- Down-Regulation of Inhibitor of Apoptosis Proteins by Deguelin Selectively Induces Apoptosis in Breast Cancer CellsMolecular Pharmacology, 2006
- Antibody Immunity to the p53 Oncogenic Protein Is a Prognostic Indicator in Ovarian CancerJournal of Clinical Oncology, 2006
- Cyclin B1 and Other Cyclins as Tumor Antigens in Immunosurveillance and Immunotherapy of CancerCancer Research, 2006
- Detection of autoantibodies to survivin and livin in sera from patients with breast cancerClinica Chimica Acta; International Journal of Clinical Chemistry, 2005
- Immunogenic Hsp-70 Is Overexpressed in Colorectal Cancers With High-Degree Microsatellite InstabilityDiseases of the Colon & Rectum, 2005
- Recombinant Tumor-Associated MUC1 Glycoprotein Impairs the Differentiation and Function of Dendritic CellsPublished by The American Association of Immunologists ,2005
- Human tumor cell lysates as a protein source for the detection of cancer antigen-specific humoral immunityJournal of Immunological Methods, 2005
- Effect of Dose on Immune Response in Patients Vaccinated With an HER-2/neu Intracellular Domain Protein—Based VaccineJournal of Clinical Oncology, 2004
- Generation of T-Cell Immunity to the HER-2/neu Protein After Active Immunization With HER-2/neu Peptide–Based VaccinesJournal of Clinical Oncology, 2002
- Induction of anti-self-immunity to cure cancerCell, 1995