Interferon gamma but not tumor necrosis factor alpha decreases susceptibility of human renal cell cancer cell lines to lymphokine-activated killer cells.

Abstract

Human renal cell cancer (RCC) cell lines, ACHN and KRC/Y, with or without exposure to cytokines, were examined for their susceptibility to lymphokine-activated killer (LAK) cells. Flow-cytometric analysis demonstrated constitutional expression of class I antigen on both cell lines, which was enhanced by interferon alpha (IFN alpha), IFN gamma and tumor necrosis factor alpha (TNF alpha). A 4-h 51Cr-release cytotoxicity assay demonstrated that pretreatment of both cell lines with IFN gamma or IFN alpha, but not with TNF alpha, decreased their susceptibility to LAK cells. IFN gamma also decreased susceptibility to natural killer cells in a 16-h 51Cr-release cytotoxicity assay. IFN gamma treatment decreased the susceptibility of ACHN cells in a dose-dependent manner. "Cold"-target competition assay clearly showed that IFN gamma- but not TNF alpha-pretreated cells compete less effectively than do untreated target cells. Pretreatment with IFN gamma, however, increased expression of intercellular adhesion molecule-1 (ICAM-1) to a degree comparable to that with TNF alpha. Northern blot analyses using a 520-base-pair ICAM-1 cDNA as a probe demonstrated that more 3.3-kb mRNA is expressed in IFN gamma- and TNF alpha-pretreated cells. These results suggest that IFN gamma-treated RCC cell lines may reduce their ability to be recognized by LAK cells, and that IFN-induced protection of RCC cell lines against LAK cells may depend upon a mechanism independent of the expression of class I antigens or ICAM-1 on tumor cells.