Interferon-induced increase in sensitivity of ovarian cancer targets to lysis by lymphokine-activated killer cells: selective effects on HER2/neu-overexpressing cells

• Published in: Cancer research (Chicago, Ill.) Vol. 52; no. 4; pp. 764 - 769
• Main Authors: Fady, C, Gardner, A M, Gera, J F, Lichtenstein, A
• Format: Journal Article
• Language: English
• Published: United States 15.02.1992
• Subjects: Cell Line; Cytotoxicity, Immunologic - drug effects; Dose-Response Relationship, Drug; Female; Flow Cytometry; Humans; In Vitro Techniques; Interferon-gamma - pharmacology; Killer Cells, Lymphokine-Activated - drug effects; Killer Cells, Lymphokine-Activated - immunology; Ovarian Neoplasms - immunology; Protein-Tyrosine Kinases - metabolism; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Proto-Oncogenes; Receptor, ErbB-2; Recombinant Proteins
• ISSN: 0008-5472

Overexpression of the HER2/neu oncogene in ovarian tumor cells is associated with relative resistance to lymphokine-activated killer (LAK) cell cytotoxicity. Treatment with gamma-interferon (IFN-gamma) (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-gamma and still present 24 h after removing IFN-gamma. In contrast, enhanced lysis required 3 days of exposure to IFN-gamma and was reversed within 24 h after removal of IFN-gamma. These data indicate that, although ICAM-1 is necessary, it is not sufficient for the IFN-gamma-induced enhancement of sensitivity to LAK lysis.