Decreased antigen presentation by dendritic cells in patients with breast cancer.
We evaluated T-cell responses to mitogens and to defined antigens in breast cancer patients. Significant defects in responses to tetanus toxoid and influenza virus were observed in patients with advanced-stage breast cancer. To define whether these defects were associated with a defect in antigen presentation [dendritic cells (DCs)] or effector function (T cells), these cells were studied separately. Purified DCs from 32 patients with breast cancer demonstrated a significantly decreased ability to stimulate control allogeneic T cells, but stimulation of patient T cells with either control allogeneic DCs or immobilized anti-CD3 antibody resulted in normal T-cell responses, even in patients with stage IV tumors. These data suggest that reduced DC function could be one of the major causes of the observed defect in cellular immunity in patients with advanced breast cancer. We then tested whether stem cells from these patients could give rise to functional DCs after in vitro growth with granulocyte/macrophage colony-stimulating factor and interleukin 4. Normal levels of control allogeneic and tetanus toxoid-dependent T-cell proliferation were observed when DCs obtained from precursors were used as stimulators. Those cells also induced substantially higher levels of influenza virus-specific CTL responses than mature DCs from the peripheral blood of these patients, although responses did not quite reach control values. Thus, defective T-cell function in patients with advanced breast cancer can be overcome by stimulation with DCs generated from precursors, suggesting that these cells may better serve as autologous antigen carriers for cancer immunotherapy than mature peripheral blood DCs.
Gabrilovich
D I
DI
The Vanderbilt Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-6838, USA.
Corak
J
J
Ciernik
I F
IF
Kavanaugh
D
D
Carbone
D P
DP
D001943:Breast Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006681:HLA-D Antigens / Q000032:analysis; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D006801:Humans; D008213:Lymphocyte Activation; D009367:Neoplasm Staging; D013601:T-Lymphocytes / Q000276:immunology*
D006681:HLA-D Antigens; D015395:Histocompatibility Antigens Class I