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.
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.
Ko
Byung K
BK
Department of General Surgery, College of Medicine, Ulsan University Hospital, Ulsan, Korea. kobyky59@yahoo.com
Efferson
Clay L
CL
Kawano
Kouichiro
K
Kuerer
Henry M
HM
Sahin
Aysegul
A
Murray
James L
JL
Ioannides
Constantin G
CG
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
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