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

干扰素-G对人结肠癌细胞株HT-29的作用 通过未激活的单核细胞增加其对裂解的易感性。因为我们 以前曾观察到某些黏附分子在 单核细胞介导的细胞毒性，我们想要确定这种活性是否 由于肿瘤细胞表面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 经干扰素-γ或肿瘤坏死因子治疗后增加(超过150%)。干扰素-α， 然而，IL-1和GM-CSF治疗对ICAM-1只有轻微的影响 表情。同样，当用干扰素-γ或干扰素-γ处理HT-29细胞时 肿瘤坏死因子，单核细胞介导的细胞毒性显著 而干扰素-α、IL-1或GM-CSF对此无影响。 而抗ICAM-1抗体并不能抑制10-20%的基线杀伤 未经处理的HT-29细胞，抗ICAM-1抗体确实抑制了 干扰素-γ或肿瘤坏死因子增强对HT-29细胞的杀伤作用 前处理。因此，某些细胞因子可以增加ICAM-1的表达 从而增加肿瘤细胞对单核细胞裂解的敏感性。

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.