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Interleukin-4 gene transduced tumor cells promote a potent tumor-specific Th1-type response in cooperation with interferon-α transduction
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Description
To investigate antitumor mechanisms in interleukin (IL)-4 therapy, we established an IL-4-overexpressing MC38 murine colorectal cancer cell line (MC38-IL4). As a therapy against established tumors, MC38-IL4 cells were inoculated contralaterally 7 days after wild-type (MC38-WT) cells had been injected, significantly reducing growth of wild-type tumors (P=0.030). Immunohistochemical analysis showed numerous granulocytes infiltrating wild-type tumors of MC38-IL4-inoculated mice. Injection of MC38-IL4 cells in leukocyte-depleted mice confirmed that granulocytes were involved in IL-4-related primary antitumor effects. Inoculation of MC38-WT in leukocyte-depleted mice initially injected with MC38-IL4 suggested that T cells contributed to the antitumor effects. To investigate tumor-specific responses, we stimulated splenocytes of MC38-immune mice with MC38-IL4 cells in vitro, resulting in MC38-specific lysis (57.5+/-7.2%, effector to target ratio=20). Treatment of established wild-type tumors with MC38-IL4 in combination with interferon (IFN)-alpha-overexpressing MC38 cells (MC38-IFNalpha) significantly reduced the growth of wild-type tumors (P=0.009). In vitro IFN-gamma production by splenocytes from mice injected with both MC38-IL4 and -IFNalpha was greatly enhanced in comparison with MC38-IL4 alone, while IL-10 production was not increased. Thus, granulocytes concern early antitumor effects of IL-4 therapy. Subsequently, IL-4 induces long-lasting, tumor-specific immune responses. IL-4 appears to promote a T-helper 1-type antitumor immune response, which is enhanced in cooperation with IFN-alpha.
Journal
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- Gene Therapy
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Gene Therapy 12 733-741, 2005-03-17
Springer Science and Business Media LLC
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Keywords
- Cytotoxicity, Immunologic
- Immunity, Cellular
- Interferon-alpha
- Genetic Therapy
- Th1 Cells
- Interleukin-12
- Interleukin-10
- Mice, Inbred C57BL
- Interferon-gamma
- Mice
- Transduction, Genetic
- Tumor Cells, Cultured
- Animals
- Female
- Interleukin-4
- Colorectal Neoplasms
- Neoplasm Transplantation
- Spleen
- T-Lymphocytes, Cytotoxic
Details 詳細情報について
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- CRID
- 1873961342696290560
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- ISSN
- 14765462
- 09697128
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- PubMed
- 15772692
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- Data Source
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- OpenAIRE