title: Interleukin-21 activates cytotoxic T lymphocytes and natural killer cells to generate antitumor response in mouse renal cell carcinoma.
abstract: OBJECTIVE
  We evaluated the antitumor effects of IL-21 gene transfer into mouse RenCa renal cell carcinoma cells, so that cells could spontaneously secrete IL-21. We also investigated the mechanisms underlying this antitumor effect.
  
  
  METHODS
  The IL-21 gene was introduced into RenCa cells by the liposome mediated method using Lipofectamine. The in vivo antitumor effect of IL-21 secreting RenCa cells was assessed by subcutaneous injection into syngeneic BALB/c mice. Mechanisms underlying the antitumor effects were investigated in syngeneic mice in which CD8 T, CD4 T or natural killer cells had been depleted using the corresponding antibody. The cytotoxic activity of splenocytes in mice injected with IL-21 secreting RenCa cells was determined using the CytoTox 96 nonradioactive cytotoxicity assay. Immunohistochemical examinations were performed to investigate infiltrating cells around tumor sites in vivo. Tumor vaccine study was also performed.
  
  
  RESULTS
  IL-21 secreting RenCa cells were almost all rejected following subcutaneous injection into syngeneic mice. The antitumor effect of IL-21 secreting RenCa cells remained in mice in which CD4 T cells had been depleted but it was totally abrogated in mice depleted of CD8 T cells or natural killer cells. Cytotoxic activities of splenocytes were higher in IL-21 secreting RenCa cell rejected mice than in parental RenCa mice. Immunohistochemical study also supported the involvement of CD8 T cells and natural killer cells in the antitumor effect of IL-21 secreting RenCa cells. Moreover, mitomycin C treated IL-21 secreting RenCa cells inhibited the growth of parental RenCa at distant site.
  
  
  CONCLUSIONS
  IL-21 secreting RenCa could be rejected in syngeneic mice by the activation of CD8 T cells and natural killer cells. Moreover, mitomycin C treated IL-21 secreting RenCa cells could work as a tumor vaccine for parental RenCa.
authors: Division of Urology, Kobe University Graduate School of Medicine, Kobe, Japan. m_m_m_kuma@ybb.ne.jp
authors: Masafumi
authors: M
authors: Kumano
authors: Isao
authors: I
authors: Hara
authors: Junya
authors: J
authors: Furukawa
authors: Shuntaro
authors: S
authors: Oniki
authors: Hiroshi
authors: H
authors: Nagai
authors: Hideaki
authors: H
authors: Miyake
authors: Masato
authors: M
authors: Fujisawa
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D018014:Gene Transfer Techniques; D007378:Interleukins / Q000235:genetics / Q000502:physiology*; D007680:Kidney Neoplasms / Q000235:genetics / Q000276:immunology*; D007694:Killer Cells, Natural / Q000502:physiology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014161:Transduction, Genetic; D000098546:Interleukin-21
chemical_list: D019496:Cancer Vaccines; D007378:Interleukins; D000098546:Interleukin-21