Expression of the adhesion molecules ICAM-1 and ICAM-2 on tumor cell lines does not correlate with their susceptibility to natural killer cell-mediated cytolysis: evidence for additional ligands for effector cell beta integrins

Abstract

The LFA-1 molecule (CD11a/CD18), a member of the leukocyte (beta 2) integrin subfamily of the integrin supergene family, has been shown to subserve important function(s) in natural killer (NK) and lymphokine-activated killer (LAK) effector cells based on monoclonal antibody inhibition and other studies. Presently, two cellular ligands for LFA-1 have been identified, termed ICAM-1 and ICAM-2. In this study, we have examined the role of target cell ICAM-1 (CD54) and ICAM-2 in NK-mediated target lysis. Using a panel of tumor target cell lines, ICAM-1 surface protein and transcript expression did not correlate with sensitivity to NK lysis. Compared to ICAM-1, ICAM-2 transcript expression was very low or undetectable in tumor cell targets, and also did not correlate with sensitivity to NK lysis. ICAM-1+ K562 cells and K562 cells which were rendered surface ICAM-1- with an antisense oligonucleotide were equally sensitive to NK lysis. Finally, human ICAM-1- P815 cells were stably transfected with the human ICAM-1 gene, and both ICAM-1- P815 (wild type) and ICAM-1+ stable transfectants were equally insensitive to NK lysis. These studies provide evidence that ICAM-1 and ICAM-2 are not important target cell ligands for NK effector cell LFA-1 and that other target cell ICAM may exist.