DECREASED ANTIGEN PRESENTATION BY DENDRITIC CELLS IN PATIENTS WITH BREAST-CANCER

We evaluated T-cell responses to mitogens and to defined antigens in b reast cancer patients, Significant defects in responses to tetanus tor oid 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 fun ction (T cells), these cells were studied separately. Purified DCs fro nt 32 patients with breast cancer demonstrated a significantly decreas ed ability to stimulate control allogeneic T cells, but stimulation of patient T cells with either control allogeneic: DCs or immobilized an ti-CD3 antibody resulted in normal T-cell responses, even in patients with stage IV tumors. These data suggest that reduced DC function coul d be one of the major causes of the observed defect in cellular immuni ty in patients with advanced breast cancer, We then tested whether ste m cells from these patients could give rise to functional DCs after in vitro growth with granulocyte/ macrophage colony-stimulating factor a nd interleukin 4, Normal levels of control allogeneic and tetanus toxo id-dependent T-cell proliferation were observed when DCs obtained from precursors were used as stimulators, Those cells also induced substan tially higher levels of influenza virus-specific CTL responses than ma ture DCs from the peripheral blood of these patients, although respons es did not quite reach control values, Thus, defective T-cell function in patients with advanced breast cancer can be overcome by stimulatio n with DCs generated from precursors, suggesting that these cells may better serve as autologous antigen carriers for cancer immunotherapy t han mature peripheral blood DCs.