Antitumor activity of monocyte-macrophages and its potentiation in cancer patients

本研究旨在阐明人活化的巨噬细胞杀伤肿瘤细胞的机制。由ifn - γ和合成佐剂的协同作用诱导的膜相关interieukin 1α (il - 1α)被发现是人单菌介导的肿瘤细胞杀伤的介质。人肺泡巨噬细胞和单核细胞来源的巨噬细胞比血超声细胞更能产生细胞相关的IL-1alpa活性和肿瘤坏死因子（TNF）。我们还发现，人单核细胞介导的对人塞拉纳（A375）细胞的细胞毒性部分是由一种新的肿瘤细胞毒性因子介导的（KW, 30,000; PI 6），不同于IL-1和tmf - α。分析了肺癌患者血单核细胞表达抗肿瘤活性和产生IL-1的能力。肺癌的存在显著增加了血单核细胞的数量。与那些健康的供者相比，这些单核细胞的自发灭瘤活性略高。然而，两组之间IL-1的产生没有差异。在合成免疫佐剂孵育后，肺癌患者的血液单核细胞比健康供者的细胞趋向性低，但在脂质体免疫佐剂激活后，其毒性与健康供者相同。人ii -2激活的杀伤细胞对肺泡巨噬细胞和由血液超声细胞中GM-CSF成熟的巨噬细胞具有细胞毒性。这些观察结果表明，肺泡巨噬细胞可能通过产生细胞相关的il -1 α和INF，在肺部炎症和免疫反应的原位调节中发挥关键作用。

The present studies were performed to elucidate the mechaniss by which human activated mosocyte-macrophages kill tumor cells. Membrane-associated interieukin 1alpha (IL-1alpha ) induced by synergistic actions of IFN-gamma and synthetic adjutant, was found to be a mediator of human monodyte-mediated tumor cell killing. Human alveolar macrophages and monocyte-derived macrophages had abilities to produce cell-associated IL-1alpa activity and tamior necrosis factor (TNF) more than blood sonocytes. We also found that human monocyte-mediated cytotoxicity against human selanona (A375) cells was mediated in part by a new tumor cytotoxic factor (KW, 30,000; PI 6), differing from IL-1 and TMF-alpha. Abilities of blood monocytes of lung cancer patients to express antitamor activity and to produce IL-1 were analyzed. The presence of lung cancer significantly increased the number of barvested blood monocytes. Spontaneous tumoricidel activity of these monocutes was slightly high as compared to those of healthy donors. Nevertheless, there was no difference in production of IL-1 between two groups. Blood monocutes of lung cancer patients were less cytotaxic than healthy donors subsequent to incubation with synthetic immunoadjuvant, but were as tomoricidal as those from healthy donors when activated with liposome-entrapped immunoadjuvant. Human II-2-activated killer cells were cytotoxic to alveolar macrophages and to macrophates matured by GM-CSF from blood sonocytes. These observations suggest that alveolar macrophages may play a critical role in situ regulation of pulmonary inflammatory and immune reactions through production of cell- associated IL-1alpha and INF.