Role of LFA-3, ICAM-1, and MHC Class I on the Sensitivity of Human Tumor Cells to LAK Cells

Abstract

Cellular adhesion molecules have been shown to be involved in tumor cell killing by cytotoxic cells such as natural killer (NK), lymphokine-activated killer (LAK), and T cells, but the precise mechanisms involved have not been clearly determined and a single target molecule has not been identified. We have examined the relative sensitivities of a panel of human tumor cell lines to LAK cell-mediated killing, in order to correlate their sensitivities with LAK cell-tumor cell binding determined by flow cytometry, and also with expression of molecules putatively involved in both the adhesion and recognition process. Two cell adhesion molecules in the immunoglobulin supergene family lymphocyte function-associated antigen (LFA-3) and intercellular adhesion molecule (ICAM-1) expression by tumor cells were examined in detail with respect to the degree of LAK cell-tumor cell conjugation and cytotoxicity. LAK sensitivity of the tumor cell lines was not clearly related to the degree of binding and correlated most strongly with the level of LFA-3 expressed on these cell lines. Major histocompatability complex (MHC) Class I antigen (Ag) expression by tumors was also examined and correlated with an inhibitory effect on LAK cell-mediated killing. Interferon-γ(IFN) treatment of two of these tumor lines decreased their sensitivity to LAK, and treated cells exhibited a higher level of MHC Class I Ag and ICAM-1 and an increased degree of conjugation with LAK cells. These findings demonstrate roles for LFA-3, ICAM-1, and MHC Class I expression in the LAK cell-tumor cell recognition and triggering of the lytic process.