Exogenous expression of mouse interferon gamma cDNA in mouse neuroblastoma C1300 cells results in reduced tumorigenicity by augmented anti-tumor immunity.
To examine the influence of interferon gamma (IFN-gamma) on tumorigenicity, we established constitutively IFN-gamma-producing cell lines from a malignant mouse neuroblastoma, C1300, by retroviral transfer of a mouse IFN-gamma cDNA. The gene-transferred cells generally showed an enhanced high-level expression of the major histocompatibility complex class I antigens at the cell surface and the transcription levels, irrespective of their IFN-gamma-producing potential. Although in vitro cell growth of these cells was unaffected by the IFN-gamma production, their s.c. tumor growth in syngeneic A/J mice was dependent upon levels of IFN-gamma production; tumors induced by a low-producer line grew well at a rate similar to those induced by the parental one, but tumor growth of a high-producer line was strongly suppressed. This apparent tumor suppression was abolished by simultaneous i.p. injection of anti-Lyt2.2 and/or anti-IFN-gamma monoclonal antibodies, and subsequently large tumors of the high producer were generated. Anti-asialoganglioside GM1 antibodies allowed the high-producer line to induce a substantial but only transient tumor growth, whereas other antibodies, such as anti-Lyt2.1, anti-IFN-beta, and anti-activated macrophage, had no such effect. The mice immunized with the high-producer line were resistant to tumor growth of the parental cells but permitted another kind of A/J tumor line, Sa-1, to induce remarkable tumors. These results indicate that the reduced tumorigenicity of the IFN-gamma high-producer line was due to the augmented specific anti-tumor immunity, in which cytotoxic T lymphocytes seemed to play a decisive role, probably as a result of the immunomodulatory effects of the IFN-gamma derived from the tumor.
Watanabe
Y
Y
Department of Molecular and Cellular Virology, Faculty of Medicine, Kyoto University, Japan.
Kuribayashi
K
K
Miyatake
S
S
Nishihara
K
K
Nakayama
E
E
Taniyama
T
T
Sakata
T
T
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D005796:Genes; D005822:Genetic Vectors; D007371:Interferon-gamma / Q000032:analysis / Q000235:genetics*; D008285:Major Histocompatibility Complex; D051379:Mice; D008805:Mice, Inbred A; D009447:Neuroblastoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D011994:Recombinant Proteins; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000276:immunology
D011994:Recombinant Proteins; D007371:Interferon-gamma