Exogenous Expression of Mouse Interferon γ cDNA in Mouse Neuroblastoma C1300 Cells Results in Reduced Tumorigenicity by Augmented Anti-Tumor Immunity

• Published in: Proceedings of the National Academy of Sciences - PNAS 1989-12, Vol.86 (23), p.9456-9460
• Main Authors: Watanabe, Yoshihiko, Kuribayashi, Kagemasa, Miyatake, Shinichi, Nishihara, Kiyoshi, Nakayama, Ei-Ichi, Taniyama, Tadayoshi, Sakata, Tsune-Aki
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Biological and medical sciences; Cell Division; Cell growth; Cell Line; Cell lines; Female; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression; Genes; Genetic Vectors; Histocompatibility antigens class I; Interferon-gamma - analysis; Interferon-gamma - genetics; Interferons; Macrophages; Major Histocompatibility Complex; Mice; Mice, Inbred A; Neuroblastoma - genetics; Neuroblastoma - immunology; Neuroblastoma - pathology; Recombinant Proteins; RNA; T lymphocytes; Tissue, organ and graft immunology; Transfection; Tumor cell line; Tumor Cells, Cultured - immunology; Tumors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.86.23.9456

To examine the influence of interferon γ (IFN-γ ) on tumorigenicity, we established constitutively IFN-γ -producing cell lines from a malignant mouse neuroblastoma, C1300, by retroviral transfer of a mouse IFN-γ 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-γ -producing potential. Although in vitro cell growth of these cells was unaffected by the IFN-γ production, their s.c. tumor growth in syngeneic A/J mice was dependent upon levels of IFN-γ 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-γ 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-β , 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-γ 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-γ derived from the tumor.