Interferon-α-induced protection of renal cell cancer cell line from lysis by natural killer cells and increase of susceptibility by treatment with 5-fluorouracil

We have shown previously that interferon (IFN)-α reduces the sensitivity of renal cell cancer (RCC) cell lines ACHN and KRC/Y to lysis by lymphokine-activated killer (LAK) cells. The close relationship between natural killer (NK) cells and LAK cells prompted us to investigate whether IFN-α pretreatment also affects the sensitivity of ACHN cells to lysis by NK cells or IFN-α-activated NK cells. A 51Cr-release cytotoxicity assay demonstrated that pretreatment of ACHN with IFN-α decreased their susceptibility to NK cells and IFN-α-activated NK cells in a dose-dependent manner. Moreover, to investigate the usefulness of 5-fluorouracil (5FU) for combination with IFN-α therapy, we examined the effect of preincubation with 5FU on the susceptibility of ACHN. IFN-α-induced protection of ACHN from lysis by IFN-α-activated NK cells weakened in the presence of 5FU at 0.2μg/ml. An adhesion assay showed that preincubation of ACHN with 5FU and IFN-α did not alter the adhesion of IFN-α-activated NK cells. A cold target competition analysis did not show any difference between untreated and 5FU and/or IFN-α-treated competitors. These results suggest that one of the mechanisms of 5FU for combination with IFN-α therapy might depend on changes of RCC cells in intrinsic lysability involving a post-binding stage of the lytic cycle to NK cells.