Interferon-y-induced Intercellular Adhesion Molecule-1: Expression on Human Tumor Cells Enhances Bifunctional Antibody-mediated Lysis through a Lymphocyte Function-associated Antigen-1 Dependent Mechanism

Patrick S. Ramsey, Phillip A. Dean, Aliza Tasimowicz-Alpini, John H. Donohue, Heidi Nelson

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Antitumor x anti-CD3 bifunctional antibodies (BFAs) affect tumor cell lysis by activating and physically linking T-cells and tumor cells. Since tumor target antigen expression does not correlate with susceptibility to BFA-mediated tumor cytotoxicity, we investigated the role of cell adhesion molecules as accessory molecules. In 3 human colon tumor cell lines (LS174T, WIDR, and COLO205), recombinant interferon-y (rIFN-y) consistently increased BFA-mediated tumor cell lysis by cultured peripheral blood lymphocytes and consistently increased tumor cell expression of intercellular adhesion molecule-1 (ICAM-1). Using cell conjugation assays, we demonstrated that ICAM-1 and lymphocyte function-associated antigen-1 (LFA-1) interactions were important for effector-to-target cell conjugate formation and demonstrated that tumor cell pretreatment with rIFN-y enhanced cell conjugate formation. Whereas anti-LFA-1 blocked all BFA-mediated tumor lysis and conjugate formation, anti-ICAM-1 blocked only the enhancing effects of rIFN-y for both cytolysis and conjugate formation. Although BFAs were shown to provide effector-to-target cell bridging, LFA-1 was found to be a common critical element required for BFA-mediated cell conjugation and lysis. ICAM-1, which was augmented by rIFN-y, appears to be only one of several ligands interacting with LFA-1. These results provide one explanation as to why high expression of tumor-associated antigen alone does not predict the susceptibility to BFA-mediated lysis and provides further support for the concept of combined modality immune therapies.

Original languageEnglish (US)
Pages (from-to)4652-4657
Number of pages6
JournalCancer research
Volume53
Issue number19
StatePublished - Oct 1 1993

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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