Decreased antigen presentation by dendritic cells in patients with breast cancer.
Decreased antigen presentation by dendritic cells in patients with breast cancer.
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发表时间：
1997-03
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通讯作者：
D. Gabrilovich;Jadranco Corak;I. Ciernik;D. Kavanaugh;D. Carbone
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作者：
D. Gabrilovich;Jadranco Corak;I. Ciernik;D. Kavanaugh;D. Carbone
我们评估了乳腺癌患者对有丝分裂原和特定抗原的t细胞反应。在晚期乳腺癌患者中观察到破伤风类毒素和流感病毒应答的显著缺陷。为了确定这些缺陷是否与抗原呈递缺陷[树突状细胞（dc）]或效应功能缺陷（T细胞）有关，分别研究了这些细胞。来自32例乳腺癌患者的纯化dc刺激对照异体T细胞的能力显著降低，但用对照异体dc或固定抗cd3抗体刺激患者T细胞导致正常T细胞反应，即使在IV期肿瘤患者中也是如此。这些数据表明，DC功能降低可能是晚期乳腺癌患者细胞免疫缺陷的主要原因之一。然后，我们测试了这些患者的干细胞在粒细胞/巨噬细胞集落刺激因子和白细胞介素4的体外培养后是否能产生功能性DCs。当从前体获得的dc作为刺激剂时，观察到正常水平的对照异体和破伤风类毒素依赖性t细胞增殖。与来自这些患者外周血的成熟dc相比，这些细胞也诱导了更高水平的流感病毒特异性CTL反应，尽管反应没有完全达到控制值。因此，晚期乳腺癌患者的t细胞功能缺陷可以通过前体生成的dc刺激来克服，这表明这些细胞可能比成熟的外周血dc更好地作为癌症免疫治疗的自体抗原载体。
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.