Abstract
Breast cancer metastasizes from the primary site to the axillary lymph nodes (LN). It is unknown whether tumor metastasis abolishes or enhances the ability of LN cells to develop a specific response to the Ag expressed by the tumor, and whether an immune response to the same Ag is present in the tumor-free LN. We stimulated lymphocytes from a metastasis negative (Met-) and a metastasis positive (Met+) LN, invaded by a HER-2+ tumor, from the same patient, with HER-2 peptides E75 (369-377) and G89 (776-778). E75 define a CTL epitope presented by HLA-A2, while G89 define a CD4+ cell recognized epitope. Met- LN responded to E75+G89 with higher expansion of E75 TCR+ CD45RO+ CCR7- (CCR7-) and E75-TCR+ CD45RO+ CCR7+ (CCR7+) cells than Met+ LN. Stimulation with E75+G89 induced a significant increase in CCR7+ cells in Met- LN compared with Met+ LN. The levels of IFN-alpha and IL-15 were higher in Met- LN cultures stimulated with E75+G89 than in Met+ LN cultures. This increase did not correlate with the levels of induction of IFN-gamma, IL-4, and IL-10. The finding of higher expansion of Ag specific CCR7+ cells and of differentiation to CCR7- cells, which define the TCM and TEM subsets respectively, in Met- LN, by G89 is novel for tumor systems. This may have implications for preventative vaccination strategies for breast and ovarian cancer.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Breast Neoplasms / immunology*
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / immunology*
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Carcinoma, Ductal / immunology
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Carcinoma, Ductal / metabolism
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Carcinoma, Ductal / secondary
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Epitopes, T-Lymphocyte / immunology
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Female
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HLA-A2 Antigen / metabolism
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Humans
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Immunologic Memory*
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Interferon-alpha / metabolism
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Interferon-gamma / metabolism
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Interleukin-10 / metabolism
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Interleukin-15 / metabolism
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Interleukin-4 / metabolism
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Leukocyte Common Antigens / metabolism
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Lymph Nodes / cytology*
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Lymph Nodes / immunology
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Lymphatic Metastasis / pathology*
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Lymphocyte Activation
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Neoplasm Invasiveness / pathology
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Peptide Fragments / immunology
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Peptide Fragments / metabolism
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Receptor, ErbB-2 / immunology*
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Receptor, ErbB-2 / metabolism
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Receptors, Antigen, T-Cell / immunology
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Receptors, Antigen, T-Cell / metabolism
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Receptors, CCR7
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Receptors, Chemokine / metabolism
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T-Lymphocytes, Cytotoxic / cytology
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T-Lymphocytes, Cytotoxic / immunology*
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Tumor Cells, Cultured
Substances
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CCR7 protein, human
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Epitopes, T-Lymphocyte
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HLA-A2 Antigen
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Interferon-alpha
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Interleukin-15
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Peptide Fragments
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Receptors, Antigen, T-Cell
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Receptors, CCR7
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Receptors, Chemokine
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Interleukin-10
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Interleukin-4
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Interferon-gamma
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Receptor, ErbB-2
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Leukocyte Common Antigens