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

我们之前已经发现，ICAM-1在两个细胞上的表达增加 不同的肿瘤细胞系导致对这些物质的敏感性增加 由人类单核细胞裂解的细胞。提出的证据表明， 溶血易感性的增加是增强的直接结果 ICAM-1的表达。LFA-1与人单核细胞相互作用的研究 肿瘤细胞上的ICAM-1被发现是发生溶解所必需的。这个 这项研究的结果发表在《免疫学杂志》上， 146：3682-3686,1991。在这项工作中，我们发现 细胞因子对肿瘤细胞的作用只占 某些化合物对单核细胞介导的细胞毒作用的全面增强 细胞因子。单核细胞单独暴露于某些细胞因子会导致 LFA-1/ICAM-1相互作用的改变。有几个 单核细胞暴露于细胞因子可能改变LFA的机制-- 1/FCAM-1相互作用。我们已经排除了细胞因子 单核细胞治疗导致LFA-1表达增加。然而，我们 目前正在进行实验，以确定病毒的亲和力 LFA-1/ICAM-1的相互作用可通过细胞因子治疗或细胞因子 经预处理的单核细胞与肿瘤细胞接触后释放肿瘤坏死因子或白介素1。

We have previously found that an increase in ICAM-1 expression on two different tumor cell lines resulted in an increased sensitivity of these cells to lysis by human monocytes. Evidence was presented that the increase in vulnerability to lysis was a direct result of the enhanced expression of ICAM-1. The interactions of LFA-1 on human monocytes to ICAM-1 on tumor cells was found to be necessary for lysis to occur. The results of this work were published in The Journal of Immunology, 146:3682-3686, 1991. In the course of this work, we found that the actions of the cytokines on the tumor cells accounts for only part of the overall enhancement of monocyte-mediated cytotoxicity induced by certain cytokines. The exposure of monocytes alone to some cytokines results in an alteration of the LFA-1/ICAM-1 interactions. There are several mechanisms by which exposure of monocytes to cytokines may alter the LFA- 1/FCAM-1 interactions. We have ruled out the possibility that cytokine treatment of monocytes results in increased LFA-1 expression. However, we are currently conducting experiments to determine if the affinity of the LFA-1/ICAM-1 interaction is altered by cytokine treatment, or if cytokine pretreated monocytes release TNF or IL-1 upon contact with tumor cells.