Stimulation of cells from a non-invaded and an invaded lymph node with a HER-2+ tumor with peptides corresponding to T-cell epitopes E75 and G89 induced expansion of central memory cells (TCM) from the metastasis-negative lymph nodes

Int J Oncol. 2004 Jun;24(6):1413-8.

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

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Breast Neoplasms / immunology*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • Carcinoma, Ductal / immunology
  • Carcinoma, Ductal / metabolism
  • Carcinoma, Ductal / secondary
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • HLA-A2 Antigen / metabolism
  • Humans
  • Immunologic Memory*
  • Interferon-alpha / metabolism
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-15 / metabolism
  • Interleukin-4 / metabolism
  • Leukocyte Common Antigens / metabolism
  • Lymph Nodes / cytology*
  • Lymph Nodes / immunology
  • Lymphatic Metastasis / pathology*
  • Lymphocyte Activation
  • Neoplasm Invasiveness / pathology
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism
  • Receptor, ErbB-2 / immunology*
  • Receptor, ErbB-2 / metabolism
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, CCR7
  • Receptors, Chemokine / metabolism
  • T-Lymphocytes, Cytotoxic / cytology
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tumor Cells, Cultured

Substances

  • CCR7 protein, human
  • Epitopes, T-Lymphocyte
  • HLA-A2 Antigen
  • Interferon-alpha
  • Interleukin-15
  • Peptide Fragments
  • Receptors, Antigen, T-Cell
  • Receptors, CCR7
  • Receptors, Chemokine
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma
  • Receptor, ErbB-2
  • Leukocyte Common Antigens