title: 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.
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.
authors.affiliation: Department of General Surgery, College of Medicine, Ulsan University Hospital, Ulsan, Korea. kobyky59@yahoo.com
authors.forename: Byung K
authors.initials: BK
authors.lastname: Ko
authors.forename: Clay L
authors.initials: CL
authors.lastname: Efferson
authors.forename: Kouichiro
authors.initials: K
authors.lastname: Kawano
authors.forename: Henry M
authors.initials: HM
authors.lastname: Kuerer
authors.forename: Aysegul
authors.initials: A
authors.lastname: Sahin
authors.forename: James L
authors.initials: JL
authors.lastname: Murray
authors.forename: Constantin G
authors.initials: CG
authors.lastname: Ioannides
mesh_terms: D001943:Breast Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D044584:Carcinoma, Ductal / Q000276:immunology / Q000378:metabolism / Q000556:secondary; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D015789:HLA-A2 Antigen / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory; D016898:Interferon-alpha / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D019409:Interleukin-15 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology* / Q000276:immunology; D008207:Lymphatic Metastasis / Q000473:pathology*; D008213:Lymphocyte Activation; D009361:Neoplasm Invasiveness / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology* / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D016898:Interferon-alpha; D007371:Interferon-gamma; D016753:Interleukin-10; D019409:Interleukin-15; D015847:Interleukin-4; D017493:Leukocyte Common Antigens; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; D011948:Receptors, Antigen, T-Cell; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; C515370:CCR7 protein, human