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Interferon-induced Increase in Sensitivity of Ovarian Cancer Targets to Lysis by Lymphokine-activated Killer Cells: Selective Effects on HER2/neu-overexpressing Cells¹

Department of Medicine, V.A. Wadsworth-UCLA Medical Center, the Wadsworth V.A. Hospital and the Jonsson Comprehensive Cancer Center, Los Angeles, California 90073

Overexpression of the HER2/neu oncogene in ovarian tumor cells is associated with relative resistance to lymphokine-activated killer (LAK) cell cytotoxicity. Treatment with -interferon (IFN-) (200–2000 units/ml) for 3 days markedly enhanced the sensitivity of HER2/neu-overexpressing ovarian tumor cells to LAK cells but had no effect on the sensitivity of nonexpressing ovarian targets. Increased sensitivity to lysis was associated with an increase in effector-target conjugate formation, the induction of target cell intercellular adhesion molecule 1 (ICAM-1) expression, and the down-regulation of HER2/neu expression. Anti-ICAM-1 antibody blocked the enhanced lysis, indicating that ICAM-1 is important in the increased sensitivity to LAK cells. However, induction of ICAM-1 expression did not correlate well with enhanced sensitivity to lysis; it was maximal after 24 h of exposure to IFN- and still present 24 h after removing IFN-. In contrast, enhanced lysis required 3 days of exposure to IFN- and was reversed within 24 h after removal of IFN-. These data indicate that, although ICAM-1 is necessary, it is not sufficient for the IFN--induced enhancement of sensitivity to LAK lysis.

¹ Supported by research funds of the Veteran's Administration, California Institute for Cancer Research, and Jonsson Cancer Center Core Grant CA16042 funded by NIH.

² To whom requests for reprints should be addressed, at V.A. Wadsworth Hospital, 691/W111H, Wilshire and Sawtelle Blvds., Los Angeles, CA 90073.

Received 8/12/91. Accepted 12/ 3/91.

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