IL-10 expression by CT26 colon carcinoma cells inhibits their malignant phenotype and induces a T cell-mediated tumor rejection in the context of a systemic Th2 response

Gene Ther. 1999 Oct;6(10):1705-12. doi: 10.1038/sj.gt.3301012.

Abstract

In spite of the evidence that IL-10 has Th1-immunosuppressive and anti-inflammatory effects, it has been shown that IL-10 may reduce the tumorigenic capacity of certain tumor cell types. In order to characterize the responses elicited by IL-10, we explored the effect of transducing murine CT26 colon carcinoma cells with a recombinant retrovirus expressing mIL-10. IL-10 gene transfer of CT26 cells had no effect on tumor cell growth on plastic surface but inhibited the anchorage-independent growth capacity of tumor cells and their metastatic potential as assessed by their invasive and migration ability. Expression of IL-10 also elicited an antitumor immune response involving both CD4+ and CD8+ T cells. Assessment of the immune status of the animals demonstrated that mice injected with CT26-IL10 cells showed prevalence of a systemic and tumor-specific Th2 response. Spleen cells obtained from these mice showed an increased production of IL-4 and no changes in IFNgamma levels, characteristic of a Th2 response. These results demonstrate that IL-10 affects CT26 tumor cell growth by both inhibiting the malignant phenotype and by recruiting and activating a T cell-mediated antitumor response. This T cell response occurs in the context of a shift towards a Th2 response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Colonic Neoplasms / immunology
  • Colonic Neoplasms / therapy*
  • Flow Cytometry
  • Gene Transfer Techniques*
  • Genetic Therapy / methods*
  • Genetic Vectors / administration & dosage
  • Humans
  • Immunoglobulin G / blood
  • Interferon-gamma / immunology
  • Interleukin-10 / genetics*
  • Interleukin-10 / immunology
  • Interleukin-4 / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Invasiveness
  • Retroviridae / genetics
  • Spleen / immunology
  • Th2 Cells / immunology*
  • Tumor Cells, Cultured

Substances

  • Immunoglobulin G
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma