Kamamura Y, Takahashi K, Komaki K, Monden Y
Second Department of Surgery, University of Tokushima School of Medicine, Japan.
J Med Invest. 1998 Aug;45(1-4):71-5.
We examined the effect of recombinant IFN-alpha and IFN-gamma on induction of LAK cells from peripheral blood mononuclear cells (PBMNCs) in 7 pre-operative breast cancer patients and 4 healthy volunteers. Significant LAK activity was developed from PBMNCs of pre-operative breast cancer patients and healthy volunteers after incubation for 4 days with IL-2 (presence of IL-2 vs. absence of IL-2). Incubation of PBMNCs of pre-operative breast cancer patients with 1000 U/ml of IFN-alpha for 4 days suppressed the LAK activity significantly (P < 0.05). By contrast, incubation of PBMNCs of pre-operative patients with 1000 U/ml of IFN-gamma for 4 days increased the LAK activity significantly (P < 0.05). Significant cytotoxicity against MCF-7 cells (estrogen receptor positive human breast cancer cell line) was developed from PBMNCs of pre-operative breast cancer patients at 20:1 and 40:1 E/T ratios after incubation for 4 days with IL-2 (absence of IL-2 vs. 20:1 or 40:1, P < 0.05, P < 0.05), whereas PBMNCs of healthy volunteers did not. Stimulation of LAK cells with IFN-gamma produced a significant augmentation of cytotoxic activity against MCF-7 (P < 0.05), while IFN-alpha suppressed the cytotoxicity significantly (P < 0.05). These findings suggested that combined stimulation by IFN-gamma and IL-2 might be a reasonable treatment for breast cancer patients.
我们检测了重组干扰素-α（IFN-α）和干扰素-γ（IFN-γ）对7例术前乳腺癌患者及4名健康志愿者外周血单个核细胞（PBMNCs）诱导生成淋巴因子激活的杀伤细胞（LAK细胞）的影响。术前乳腺癌患者和健康志愿者的PBMNCs在与白细胞介素-2（IL-2）共同孵育4天后（存在IL-2与不存在IL-2的情况）产生了显著的LAK活性。术前乳腺癌患者的PBMNCs与1000 U/ml的IFN-α孵育4天可显著抑制LAK活性（P<0.05）。相比之下，术前患者的PBMNCs与1000 U/ml的IFN-γ孵育4天可显著提高LAK活性（P<0.05）。术前乳腺癌患者的PBMNCs在与IL-2孵育4天后，在效应细胞与靶细胞比例为20:1和40:1时对MCF-7细胞（雌激素受体阳性的人乳腺癌细胞系）产生了显著的细胞毒性（不存在IL-2与20:1或40:1相比，P<0.05，P<0.05），而健康志愿者的PBMNCs则未产生。用IFN-γ刺激LAK细胞可显著增强对MCF-7的细胞毒性活性（P<0.05），而IFN-α则显著抑制细胞毒性（P<0.05）。这些发现提示，IFN-γ和IL-2联合刺激可能是乳腺癌患者的一种合理治疗方法。
