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 (IFN-gamma) in H-2Kk-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-gamma) transfectants were generated and their behavior was investigated as compared to parental and IFN-gamma-transfected BW-Sp3. Although expression of huIL-2 was equally effective as IFN-gamma in preventing tumor formation and reducing experimental metastasis, it did not confer protection to spontaneous metastases and even reversed the anti-metastatic activity of IFN-gamma. Inoculation of the BW variants in immunocompromised mice revealed that expression of IL-2 activates both T cells and aspecific immune effectors. However, in immunocompromised mice a clear pro-metastatic effect of IL-2 was recorded. Analysis of membrane antigens on the different variants showed a selective effect of huIL-2 on the expression of two surface antigens, i.e. L-selectin and metastatic T cell hybridoma antigen (MTH), which may contribute to metastasis. Hence upon expression of huIL-2 in T lymphoma variants, tumor outcome will depend on the balanced effects of the transfected cytokines on the immune response and the redirected effect on tumor progression.
Geldhof
A B
AB
Laboratory of Cellular Immunology, Flanders Interuniversity Institute for Biotechnology, Free University of Brussels, Belgium.
Van Ginderachter
J
J
Vandersteen
P
P
Raes
G
G
De Baetselier
P
P
D000818:Animals; D002455:Cell Division; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007371:Interferon-gamma / Q000235:genetics* / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics* / Q000378:metabolism; D016399:Lymphoma, T-Cell / Q000276:immunology* / Q000503:physiopathology; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D008806:Mice, Inbred AKR; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D014162:Transfection
D007376:Interleukin-2; D008565:Membrane Proteins; D007371:Interferon-gamma