ENHANCEMENT OF ICAM-1 SENSITIZES TUMOR CELLS TO MONOCYTE-MEDIATED LYSIS

ICAM-1 的增强使肿瘤细胞对单核细胞介导的裂解敏感

• 批准号: 3811208
• 负责人: D S WEBB
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3811208
• 关键词: antibody dependent killer cell; colon neoplasms; colony stimulating factor; human tissue; interferons; leukocyte adhesion molecules; macrophage; monocyte; neoplasm /cancer immunology; tumor antigens; tumor necrosis factor alpha

Pretreatment of the human colon carcinoma cell line, HT-29, with IFN-G increases their vulnerability to lysis by unactivated monocytes. Because we had previously observed the importance of certain adhesion molecules on monocyte-mediated cytotoxicity, we wanted to determine if this activity was due to changes in the expression of ICAM-1 on the tumor cells. HT-29 cells expressed low levels of ICAM-1 and this expression was dramatically increased ( greater than 150%) by IFN-gamma or TNF treatment. IFN-alpha, IL-1 and GM-CSF treatment, however, had only marginal effects on ICAM-1 expression. Likewise, when HT-29 cells were pretreated with IFN-gamma or TNF, the monocyte-mediated cytotoxicity of these cells was significantly increased, while pretreatment with IFN-alpha, IL-1 or GM-CSF had no effect. While anti-ICAM-1 antibodies did not inhibit the 10-20% baseline killing of the untreated HT-29 cells, the anti-ICAM-1 antibodies did inhibit the augmented killing of the HT-29 cells observed following IFN-gamma or TNF pretreatment. Thus, certain cytokines can increase the expression of ICAM-1 on tumor cells thereby increasing their sensitivity to lysis by monocytes.

IFN-γ预处理人结肠癌细胞HT-29的实验研究 增加了它们对未活化的单核细胞裂解的脆弱性。因为我们 先前已经观察到某些粘附分子对 单核细胞介导的细胞毒性，我们想确定这种活性是否 这是由于肿瘤细胞上ICAM-1表达的变化。HT-29细胞 表达低水平的ICAM-1，并且这种表达显著地 IFN-γ或TNF治疗增加（大于150%）。IFN-α， 然而，IL-1和GM-CSF治疗对ICAM-1的影响很小 表情同样地，当HT-29细胞用IFN-γ或IFN-γ预处理时， TNF，单核细胞介导的这些细胞的细胞毒作用是显著的 而用IFN-α、IL-1或GM-CSF预处理则无影响。 虽然抗ICAM-1抗体不能抑制10-20%的基线杀伤， 在未处理的HT-29细胞中，抗ICAM-1抗体确实抑制了 在IFN-γ或TNF-α后观察到HT-29细胞的杀伤增强 预处理因此，某些细胞因子可以增加ICAM-1的表达 从而增加它们对单核细胞裂解的敏感性。