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.
