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Secretion of interleukin-10 from murine colon carcinoma cells suppresses systemic antitumor immunity and impairs protective immunity induced against the tumors

Cancer Gene Therapy volume 9, pages 109–115 (2002)Cite this article

Abstract

Interleukin-10 (IL-10) is a T helper type 2 (Th2) cytokine that suppresses Th1-mediated, cell-mediated immune responses and reciprocally enhances antibody-mediated responses. Previous studies, however, demonstrated that forced expression of the IL-10 gene in tumor cells could unexpectedly produce antitumor effects. We then examined whether tumor-derived IL-10 could modulate systemic immune responses. Murine colon carcinoma (Colon 26) cells that were retrovirally transduced with the murine IL-10 gene (Colon 26/IL-10) were inoculated in syngeneic immunocompetent or T cell–defective nude mice. Growth of Colon 26/IL-10 tumors was augmented in immunocompetent and, to less extent, in nude mice compared with that of wild-type tumors developed in respective mice. Growth of wild-type tumors was accelerated to the same level as that of Colon 26/IL-10 tumors when wild type and Colon 26/IL-10 cells were respectively inoculated in different flanks of the same immunocompetent mice. This enhanced growth of wild-type tumors was not observed in nude mice. Immunocompetent mice that had rejected IL-2– or IL-12–secreting Colon 26 cells developed protective immunity and became completely resistant to wild-type Colon 26 cells subsequently challenged. However, some of the mice that had rejected IL-2 or IL-12 producers developed Colon 26/IL-10 tumors inoculated thereafter. The present study showed that production of IL-10 from tumor cells impaired T cell– and non–T cell–mediated systemic antitumor immunity in hosts.

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Acknowledgements

We thank Dr. Takenaga for his assistance with RT-PCR. This work was supported by a grant-in-aid for scientific research from the Japan Society for the Promotion of Science, a grant-in-aid for scientific research on priority areas from the Ministry of Education, Culture, Sports, Science and Technology of Japan. R Bahar is supported by the STA fellowship from the Science and Technology Agency of Japan.

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Authors and Affiliations

  1. Division of Pathology, Chiba Cancer Center Research Institute, Chiba, Japan

    Kiyoko Kawamura, Rumana Bahar, Waka Natsume & Masatoshi Tagawa

  2. Department of Biology, Toho University, Funabashi, Japan

    Waka Natsume

  3. Chiba Cancer Center Research Institute, Chiba, Japan

    Shigeru Sakiyama

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  1. Kiyoko Kawamura
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  2. Rumana Bahar
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  3. Waka Natsume
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  4. Shigeru Sakiyama
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  5. Masatoshi Tagawa
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Correspondence to Masatoshi Tagawa.

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Kawamura, K., Bahar, R., Natsume, W. et al. Secretion of interleukin-10 from murine colon carcinoma cells suppresses systemic antitumor immunity and impairs protective immunity induced against the tumors. Cancer Gene Ther 9, 109–115 (2002). https://doi.org/10.1038/sj.cgt.7700418

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