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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 Therapy volume 6, pages 1705–1712 (1999)Cite this article

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 IFNγ 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.

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Acknowledgements

This work was supported in part by grants from Fundación Rene Baron, Argentina (to OLP), The Arthritis and Rheumatism Council of Great Britain (to YC), by an ICRETT (UICC) and Royal Society (United Kingdom) fellowship awarded to OLP, a joint grant from Fundación Antorchas and The British Council, Argentina (to OLP) and a grant from the National Council of Scientific and Technological Research of Argentina, CONICET (to OLP). OLP and ECH are members of the Research Career of CONICET. MFL is a fellow of CONICET. SA is a fellow of the University of Buenos Aires. We are indebted to Dr Rizgar Mageed, from the Kennedy Institute, London, for providing us with all the reagents for assessment of Ig levels. We thank L Alonso for typing the manuscript.

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Authors and Affiliations

  1. Gene Therapy Laboratory, Instituto de Investigaciones Bioquímicas Fundación Campomar, CONICET, FCEYN, Universidad de Buenos Aires, Argentina

    S K Adris, M F Ledda & O L Podhajcer

  2. Instituto de Oncologia Angel H Roffo, Argentina

    S Klein & M A Jasnis

  3. Hospital de Clínicas Jose de S Martín, Argentina

    E Chuluyan

  4. Hospital E. Perón, Argentina

    A I Bravo

  5. Facultad de Veterinaria, Universidad de La Plata, Argentina

    C Carbone

  6. Kennedy Institute of Rheumatology, London, UK

    Y Chernajovsky

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  1. S K Adris
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Adris, S., Klein, S., Jasnis, M. et al. 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 6, 1705–1712 (1999). https://doi.org/10.1038/sj.gt.3301012

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