Munn D H, Cheung N K
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
J Exp Med. 1990 Jul 1;172(1):231-7. doi: 10.1084/jem.172.1.231.
Macrophages and cultured human monocytes can mediate efficient antibody-dependent cytotoxicity (ADCC) against human tumor cells using monoclonal antibodies (mAbs). The mechanism of this killing is usually assumed to involve secreted factors (reactive oxygen intermediates, tumor necrosis factor, or other cytotoxic factors) leading to target cell lysis. In this study, we present evidence that phagocytosis of intact target cells is the principal mechanism of antitumor cytotoxicity in our in vitro model of ADCC by cultured monocytes. Human monocytes cultured in recombinant human macrophage colony-stimulating factor ingested up to 100% of fluorochrome-labeled melanoma and neuroblastoma target cells, in the presence of an appropriate antitumor mAb. Electron microscopy demonstrated phagocytosis of intact tumor cells by cultured monocytes during ADCC. All of the radionuclide in radiolabeled target cells was taken up by monocytes during phagocytosis. By preventing the release of radioisotope tracers, phagocytosis thus prevents the detection of this very efficient form of cytotoxicity by most conventional assays.
巨噬细胞和培养的人单核细胞可使用单克隆抗体（mAb）介导针对人肿瘤细胞的高效抗体依赖性细胞毒性（ADCC）。通常认为这种杀伤机制涉及分泌因子（活性氧中间体、肿瘤坏死因子或其他细胞毒性因子）导致靶细胞裂解。在本研究中，我们提供证据表明，在我们培养的单核细胞ADCC体外模型中，完整靶细胞的吞噬作用是抗肿瘤细胞毒性的主要机制。在重组人巨噬细胞集落刺激因子中培养的人单核细胞，在存在适当抗肿瘤mAb的情况下，可摄取高达100%的荧光染料标记的黑色素瘤和神经母细胞瘤靶细胞。电子显微镜显示，在ADCC过程中，培养的单核细胞可吞噬完整的肿瘤细胞。在吞噬过程中，放射性标记靶细胞中的所有放射性核素都被单核细胞摄取。通过阻止放射性同位素示踪剂的释放，吞噬作用因此阻止了大多数传统检测方法对这种非常有效的细胞毒性形式的检测。
