Inhibitors of cytotoxic T cell activities produced by cultured tumor cells.

据报道，恶性肿瘤患者具有缺陷的细胞免疫状态。我们推测这种缺陷是由肿瘤细胞产生可溶性免疫抑制因子引起的。我们建立了无血清培养系统诱导高细胞毒性淋巴因子激活杀伤细胞（LAK）。利用该系统，我们研究了几种生长因子、激素和几种肿瘤细胞调节的培养基对LAK细胞生长和细胞毒活性的影响。实验结果如下：在添加白细胞介素-2、人转铁蛋白、2-巯基乙醇、2-氨基乙醇和亚硒酸钠的RD培养基中诱导的LAK细胞对肿瘤细胞的细胞毒活性比添加人血清培养基中的LAK细胞高3 ~ 4倍。胰岛素或胰岛素样生长因子- i （IGF-I）是由许多肿瘤细胞产生的自分泌或旁分泌生长因子，可抑制LAK细胞的细胞毒活性。转化生长因子- β (tgf - β)抑制LAK细胞的生长和细胞毒活性。以培养的口腔鳞癌细胞（SCC）和恶性黑色素瘤细胞（MM）为条件的培养基抑制LAK细胞的生长和细胞毒活性。理化分析表明，SCC具有耐热和耐酸抑制活性，而MM具有耐热和耐酸抑制活性。这些结果表明，SCC的活性与MM.6不同。我们用肝素-sepharose亲和色谱法分离了SCC衍生活性。结果表明，用0.9 ~ 1.2 m NaCl洗脱后，其活性显著高于tgf - β和胰岛素。

It has been reported that patients with malignant tumors have a defective cellularimmune status. We have speculated that this defect was resulted from the production of soluble immuno-suppressive factors produced by tumor cells.We have established serum-free culture system to induce highly cytotoxic lymphokine activated killer (LAK)cells. Using this system, we have studied several growth factors, hormons and medium conditioned by several tumor cells on the growth and cytotoxic activities of LAK cells. Following results were obtained.1. The LAK cells induced in RD medium supplemented with interleukin-2, human transferrin, 2-mercaptoethanol, 2-aminoethanol and sodium selenite had 3 to 4 times higher cytotoxic activities against tumor cells than the LAK cells in human serum supplemented medium.2. Insulin or insulin like growth factor-I(IGF-I) which has been produced by many tumor cells as an autocrine or a paracrine growth factor inhibited cytotoxic activities of LAK cells.3. Transforming growth factor-beta (TGF-beta) inhibited both of the growth and cytotoxic activities of LAK cells.4. The medium conditioned by cultured squamous carcinoma cells (SCC) and malignant melanoma cells(MM) derived from oral region inhibited both of the growth and cytotoxic activities of LAK cells.5. Physical and chemical analysis revealed that the suppressive activities of SCC were heat- and acid-resistant but those of MM were heat- and acid-labile. These results suggest that the activities of SCC were different from those of MM.6. We have fractionated SCC derived activities by heparin-sepharose affinity chromatography. It has been revealed that the fractions which were eluted with 0.9-1.2M NaCl exhibited significant activities which were different from TGF-beta and insulin.