含氮二膦酸盐/IL-2诱导肿瘤患者外周血γδT细胞增殖的作用

Proliferation of γδT cells induced by IL-2 and bisphosphonates-treatment in patients with cancer

目的探讨药物(含氮二膦酸盐联合IL-2,N-BP/IL-2)诱导实体肿瘤患者外周血γδT细胞增殖作用。方法采用流式细胞仪测定103例肿瘤患者和43例健康人外周血总T细胞绝对值、γδT细胞绝对值和相对值,测定患者外周血经药物体外刺激后γδT细胞增殖指数和用药前后患者外周血总T细胞、γδT细胞绝对值和相对值。结果肿瘤患者和健康人外周血总T细胞绝对值、γδT细胞绝对值和γδT细胞相对值的中位数,分别为1306细胞/μl和1522细胞/μl(P=0.003),64细胞/μl和162细胞/μl(P<0.001),5%和11%(P<0.001)。24例经药物体外扩增试验阳性的肿瘤患者治疗前后体内外周血总T细胞绝对值、γδT细胞绝对值和γδT细胞相对值的中位数,分别为1283细胞/μl和1552细胞/μl(P=0.001),54细胞/μl和107细胞/μl(P<0.1301),6%和8%(P=0.008)。全部肿瘤患者中外周血γδT细胞对药物体外诱导增殖反应阳性患者的百分率为68.9%。结论肿瘤患者外周血γδT细胞计数显著低于健康人。不同肿瘤患者外周血γδT细胞对药物刺激增殖的反应性不同。N-PB/ IL-2在体内有显著增加γδT细胞数量的药理作用。体外增殖试验可作为N-PB/IL-2治疗患者的参考。

Objective To investigate the proliferation function of gamma delta T cells by IL-2 and nitrogen containing-bisphosphonates（N-BP）-stimulated on patients with cancer. Methods We analyzed 103 patients with cancer and 43 healthy individuals. Gamma delta T cells proliferation assay in vivo determine the absolute count of gamma delta T cells before and after treatment by flow cytometry. Gamma delta T cells proliferation assay in vitro determines the relative count of gamma delta T cells after IL-2 and N-BP-stimulated by flow cytometry. Results In patients with cancer and healthy individuals, the median of the absolute count of all T cells, gamma delta T cells and the percent of gamma delta T cells were 1306 cells/μl vs 1522 cells/μl （ P = 0.003）, 64 cells/μl vs 162 cells/μl （P 〈0.001）, 5% vs 11%（P 〈 0.001）. In 24 patients treated circulating the median of the absolute count of all T cells, gamma delta T cells and the percent of gamma delta T cells were 1283 cells/μl vs 1552 cells/μl（P = 0.001 ）, 54 cells/μl vs 107 cells/μl （P 〈 0.001 ）, 6% vs 8 % （P = 0.008）. The clinical response rate to IL-2 and N-BP-sfimulated were 68.9% in all patients with cancer. Conclusion The function of gamma delta T cells proliferation is defective in the patients with cancer. The clinical response was different to IL-2 and N- BP-stimulated in differentiating patients with cancer individuals. The function of gamma delta T cells proliferation may be stimulated by IL-2 and N-BP. The gamma delta T cells proliferation assay in vitro may be applied to a target of treatment by IL-2 and N-BP-stimulated.