Atagi S, Sone S, Fukuta K, Ogura T
Third Department of Internal Medicine, University of Tokushima School of Medicine.
Jpn J Cancer Res. 1992 Oct;83(10):1088-94. doi: 10.1111/j.1349-7006.1992.tb02726.x.
We examined the effect of fibrin coagulation on tumor cytotoxicity mediated by human lymphokine (IL-2)-activated killer (LAK) cells. LAK cells were induced from peripheral blood mononuclear cells (MNC) by culture with recombinant IL-2 for 4 or 5 days, and LAK cell-mediated cytotoxicity against tumor cells was assessed by 51Cr release assay in the presence or absence of plasma from normal subjects and lung cancer patients. Plasma did not affect the phase of induction of LAK activity by IL-2, but dose-dependently inhibited the effector phase of LAK cell-mediated cytotoxicity against Daudi cells. Similar inhibition of LAK cell-mediated cytotoxicity was observed on pretreatment of Daudi cells and human lung cancer cell lines with human fibrinogen plus thrombin. A parallel relationship was found between the amount of fibrinogen in plasma of lung cancer patients and inhibition of LAK cytotoxicity. This inhibition was reduced by addition of anticoagulants (heparin or argatroban). These findings suggest that fibrin coagulation on tumor cells protects them from LAK cell-mediated tumor cytotoxicity in malignant lesions and that a combination of an anticoagulant drug and IL-2/LAK therapy may be effective for treatment of lung cancer patients.
我们研究了纤维蛋白凝血对人淋巴因子（IL-2）激活的杀伤（LAK）细胞介导的肿瘤细胞毒性的影响。通过用重组IL-2培养4或5天，从外周血单个核细胞（MNC）诱导出LAK细胞，并在有或无正常受试者和肺癌患者血浆的情况下，通过51Cr释放试验评估LAK细胞对肿瘤细胞的细胞毒性。血浆不影响IL-2诱导LAK活性的阶段，但剂量依赖性地抑制LAK细胞对Daudi细胞介导的细胞毒性的效应阶段。在用人类纤维蛋白原加凝血酶预处理Daudi细胞和人肺癌细胞系后，观察到对LAK细胞介导的细胞毒性有类似的抑制作用。在肺癌患者血浆中的纤维蛋白原量与LAK细胞毒性的抑制之间发现了平行关系。加入抗凝剂（肝素或阿加曲班）可减少这种抑制作用。这些发现表明，肿瘤细胞上的纤维蛋白凝血可保护它们免受恶性病变中LAK细胞介导的肿瘤细胞毒性，并且抗凝药物与IL-2/LAK疗法联合使用可能对肺癌患者的治疗有效。
