5-Fluorouracil increases susceptibility of renal cell cancer cell lines to lymphokine-activated killer cells: evidence for alteration not at the level of recognition but at a post-binding stage of the lytic cycle.

To investigate the usefulness of 5-Fluorouracil (5FU) for combination with immunotherapy, we examined the effect of preincubation with 5FU on the susceptibility of a renal cell cancer (RCC) cell line, ACHN, to lymphokine-activated killer (LAK) cells. A 4-h 51Cr release assay showed a remarkable increase in the susceptibility of ACHN cells to LAK cells. Dose response experiments demonstrated that 5FU at concentrations as low as 0.002 microgram/ml increased susceptibility to LAK cells. Presence of 5FU at 2 micrograms/ml but not at 0.2 microgram/ml in media blocked LAK activity induction by IL-2. Furthermore, an adhesion assay showed that preincubation with 5FU did not alter the adhesion of LAK cells to tumor cells nor the expression of intercellular adhesion molecule-1 (ICAM-1), lymphocyte function-associated antigen-3 (LFA-3) or major histocompatibility complex (MHC) class I molecules on tumor cells. Cold target competition did not show any difference between 5FU-treated and untreated competitors. These results suggest that increased susceptibility of RCC cells to LAK cells due to preincubation with 5FU might depend on changes in intrinsic lysability involving a post-binding stage of the lytic cycle.