Multiple effects of transfection with interleukin 2 and/or interferon gamma on the behavior of mouse T lymphoma cells

We have previously reported that transfection of mouse interferon gamma (IF N-gamma) in H-2K(k)-positive BW variants (BW-Sp3) abolishes tumorigenicity and reduces metastatic capacity. To further increase the immunogenicity of BW-Sp3 cells, the gene for human interleukin 2 (huIL-2) was transfected in these cancer cells, Single BW-Sp3(huIL-2) and double BW-Sp3(huIL-2+IFN-gamm a) transfectants were generated and their behavior was investigated as comp ared to parental and IFN-gamma-transfected BW-Sp3, Although expression of h uIL-2 was equally effective as IFN-gamma in preventing tumor formation and reducing experimental metastasis, it did not confer protection to spontaneo us metastases and even reversed the anti-metastatic activity of IFN-gamma, Inoculation of the BW variants in immunocompromised mice revealed that expr ession of IL-2 activates both T cells and aspecific immune effecters. Howev er, in immunocompromised mice a clear pro-metastatic effect of IL-2 was rec orded, Analysis of membrane antigens on the different variants showed a sel ective effect of huIL-2 on the expression of two surface antigens, i.e. L-s electin and metastatic T cell hybridoma antigen (MTH), which may contribute to metastasis, Hence upon expression of huIL-2 in T lymphoma variants, tum or outcome will depend on the balanced effects of the transfected cytokines on the immune response and the redirected effect on tumor progression. (C) 1998 Kluwer Academic Publishers.