Axillary Lymph Node Cellular Immune Response to HER-2/neuPeptides in Patients with Carcinoma of the Breast
- 1 May 2002
- journal article
- research article
- Published by Mary Ann Liebert Inc in Journal of Interferon & Cytokine Research
- Vol. 22 (5) , 583-592
- https://doi.org/10.1089/10799900252982061
Abstract
HER-2/neu peptides have recently been shown to induce a proliferative response by peripheral CD4+ T cells in breast cancer patients. To investigate potential differences in the local cellular immune response between breast cancer patients with and without nodal metastases, lymphocytes were isolated from axillary lymph nodes from patients with breast cancer, and proliferative and cytokine responses to HER-2/neu peptides were determined. Freshly isolated lymphocytes from lymph nodes of 7 women undergoing surgery for invasive breast cancer were plated at 20 × 105 cells per well in triplicate. Cells were stimulated with HER-2/neu peptides at 50 μg/ml and with control antigens. Incorporation of tritium-labeled thymidine was determined 4 days later. The levels of the cytokines interferon-γ (IFN-γ), interleukin-4 (IL-4), and IL-10 were determined at priming and at restimulation with HER-2/neu peptides using a cytokine-specific, double-sandwich, enzyme-linked immunosorbent assay (ELISA). Lymphocytes isolated from the axillary lymph nodes of the patients mounted significant cellular immune response to HER-2/neu peptides, manifested by proliferation and specific cytokine elaboration. Proliferative responses to HER-2/neu peptides were seen in lymphocytes of patients with and without overexpression of HER-2/neu in the primary tumor. In some patients, the proliferative response to HER-2/neu peptides in lymphocytes from lymph nodes with metastases was absent or blunted compared with the response in lymphocytes from lymph nodes without metastases from the same patient (p < 0.05). HER-2/neu peptides induced a predominantly T helper type 1 (Th1) pattern of cytokine response in nodal lymphocytes isolated from breast cancer patients. A Th1-specific cytokine production pattern was maintained at priming and restimulation with HER-2/neu peptides and was amplified with IL-12 costimulation. These results indicate that HER-2/neu peptides can activate T cells in draining lymph nodes from women with invasive breast cancer. This activation is associated with a predominantly Th1 cytokine response, which suggests that conditioning with HER-2/neu peptides may be of value in the development of breast cancer vaccines.Keywords
This publication has 18 references indexed in Scilit:
- Use of Chemotherapy plus a Monoclonal Antibody against HER2 for Metastatic Breast Cancer That Overexpresses HER2New England Journal of Medicine, 2001
- Tolerance and AutoimmunityNew England Journal of Medicine, 2001
- Immunologically ignorant autoreactive T cells, epitope spreading and repertoire limitationImmunology Today, 1995
- Identification of an immunodominant peptide of HER-2/neu protooncogene recognized by ovarian tumor-specific cytotoxic T lymphocyte lines.The Journal of Experimental Medicine, 1995
- T‐cell recognition of oncogene products: A new strategy for immunotherapyMolecular Carcinogenesis, 1992
- Studies of the HER-2/ neu Proto-Oncogene in Human Breast and Ovarian CancerScience, 1989
- Neu-Protein Overexpression in Breast CancerNew England Journal of Medicine, 1988
- Amplification of c-erbB-2 and Aggressive Human Breast Tumors?Science, 1988
- Human Breast Cancer: Correlation of Relapse and Survival with Amplification of the HER-2/ neu OncogeneScience, 1987