Allen P D, Johnston D H, Macey M G, Williams N S, Newland A C
Department of Haematology, London Hospital Medical College, Whitechapel, UK.
Anticancer Drugs. 1995 Apr;6(2):250-8. doi: 10.1097/00001813-199504000-00009.
Progressive tumor growth is associated with a state of immunosuppression. One mode of immunosuppression is thought to be mediated by immunosuppressive factors of tumour origin. We have investigated in vitro the possibility that suramin could be used to blockade tumor derived suppressor factors and enhance the effectiveness of rhIL-2 therapy. These data show that factors derived from cultures of the colorectal carcinoma cell line LoVo suppressed the percentage of cells expressing the natural killer cell antigen CD56 in 92% of individuals and the cytotoxic T cell antigen CD8 in 77% of individuals tested from a panel of 13 normal healthy volunteers. Suramin at 200 micrograms/ml restored the percentage of cells expressing CD56 to levels higher than the control cultures and reduced the suppression in those expressing CD8 to non-significant levels. LoVo produced factors also suppressed the expression of the activation associated antigens CD25, CD71 and HLA-Dr with suramin restoring CD25 expression but not CD71 or HLA-Dr. Functional studies using 51Cr-release assays showed that LoVo produced factors could suppress cytotoxicity in 46% of individuals tested, and of these a reduction in suppression by suramin was demonstrated in 50% of individuals against Daudi target cells and 33% against K562 target cells.
肿瘤的进行性生长与免疫抑制状态相关。免疫抑制的一种方式被认为是由肿瘤来源的免疫抑制因子介导的。我们在体外研究了苏拉明是否可用于阻断肿瘤衍生的抑制因子并增强重组人白细胞介素-2(rhIL-2)治疗效果的可能性。这些数据表明,来自结肠癌细胞系LoVo培养物的因子在一组13名正常健康志愿者中,使92%的个体中表达自然杀伤细胞抗原CD56的细胞百分比受到抑制,77%的个体中表达细胞毒性T细胞抗原CD8的细胞百分比受到抑制。200微克/毫升的苏拉明将表达CD56的细胞百分比恢复到高于对照培养物的水平,并将表达CD8的细胞的抑制作用降低到无统计学意义的水平。LoVo产生的因子也抑制了活化相关抗原CD25、CD71和HLA-Dr的表达,苏拉明可恢复CD25的表达,但不能恢复CD71或HLA-Dr的表达。使用51Cr释放试验的功能研究表明,LoVo产生的因子可在46%的受试个体中抑制细胞毒性,其中在50%的个体中针对Daudi靶细胞以及33%的个体中针对K562靶细胞,苏拉明可降低抑制作用。