Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Interleukin 10 (IL-10): an immunosuppressive factor and independent predictor in patients with metastatic renal cell carcinoma

This article has been updated

Summary

Interleukin 10 (IL-10) is an immunosuppressive factor and has been detected in tumour cell cultures of renal cell carcinoma and of malignant melanoma. IL-10 has been described as a cytokine of the Th2 response; it is able to suppress antigen-presenting cells (APCs) and may lead to down-regulation of HLA class I and II molecules on dendritic cells and to anergy of T-lymphocytes. We evaluated pretreatment serum levels of soluble IL-10 and various clinical parameters to determine their prognostic value in 80 advanced renal cell carcinoma patients seen at our institution between May 1990 and April 1996. For statistical evaluation we used both univariate and multivariate Cox proportional hazards models. An elevated pretreatment serum level of IL-10 was a statistically independent predictor of unfavourable outcome (P < 0.0028), in addition to the well-known clinical and biochemical risk factors. These data support risk stratification for future therapeutic trials and identify a predictor which needs to be validated in prospective studies and may potentially influence decision making in palliative management of patients with metastatic renal cell carcinoma. These data also suggest a potential role of IL-10 in the development of advanced renal cell carcinoma and in the future design of therapeutic strategies.

Change history

  • 16 November 2011

    This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication

References

  • Atzpodien, J., Lopez-Hänninen, E., Kirchner, H., Bodenstein, H., Pfreundschuh, M., Rebmann, U., Metzner, B., Illiger, H. J., Niesel, T. & Poliwoda, H. (1995). Multiinstitutional home-therapy trial of recombinant human Interleukin-2 and Interferon-α2 in progressive metastatic renal cell carcinoma. J Clin Oncol, 13(2): 497–501.

    CAS  Article  Google Scholar 

  • Blay, J-Y, Burdin, N., Rousset, F., Lenoir, G., Biron, P., Philip, T., Banchereau, J. & Favrot, M. C. (1993). Serum Interleukin-10 in non Hodgkin’s lymphoma: a prognostic factor. Blood 82: 2169–2174.

    CAS  PubMed  Google Scholar 

  • Buelens, C., Verhasselt, V., De Groote, D., Thielemans, K., Goldman, M. & Willems, F. (1997). Interleukin-10 prevents the generation of dendritic cells from human peripheral blood mononuclear cells cultured with interleukin-4 and granulocyte–macrophage-colony-stimulating factor. Eur J Immunol 27: 756–762.

    CAS  Article  Google Scholar 

  • Buer, J., Lanoue, A., Franzke, A., Garcia, C., van Boehmer, H. & Sarukhan, A. (1998). Interleukin-10 secretion and impaired effector function of MCH class ii-restricted T cells anergized in vivo. J Exp Med 187: 177–183.

    CAS  Article  Google Scholar 

  • deWaal Malefyt, R., Haanen, J. & Spits, H. (1991). Interleukin 10 and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression. J Exp Med 174: 915–924.

    CAS  Article  Google Scholar 

  • deWaal Malefyt, R., Yssel, H. & deVries, J. E. (1993). Direct effect of IL-10 on subsets of human CD4+ T cell clones and resting T cells. J Immunol 150: 4754–4765.

    CAS  Google Scholar 

  • Ding, L., Linsley, P. & Huang, L. Y. (1993). IL-10 inhibits macrophage costimulatory activity by selectively inhibiting the up-regulation of B7-expression. J Immunol 151: 1224–1234.

    CAS  PubMed  Google Scholar 

  • Dummer, W., Bastian, B. C., Ernst, N., Schanzle, C., Schwaaf, A. & Brocker, E. B. (1996). Interleukin-10 production in malignant melanoma: preferential detection of Interleukin-10-secreting tumor cells in metastatic lesions. Int J Cancer 66(5): 607–610.

    CAS  Article  Google Scholar 

  • Fiorentino, D. F., Bond, M. W. & Mosmann, T. R. (1989). Two types of mouse T helper cells. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med 170: 2081–2095.

    CAS  Article  Google Scholar 

  • Kaplan, E. L. & Meier, P. (1958). Non-parametric estimation from incomplete observations. J Am Stat Assoc 53: 457–481.

    Article  Google Scholar 

  • Knoefel, B., Nuske, K., Steiner, T., Junker, K., Kosmehl, H., Rebstock, K., Reinhold, D. & Junker, U. (1997). Renal cell carcinomas produce IL-6, IL-10, IL-11 and TGF-beta1 in primary cultures and modulate T-lymphocyte blast transformation. J Interferon Cytokine Res 17: 95–102.

    CAS  Article  Google Scholar 

  • Kruger-Krasagakes, S., Krasagakis, K., Garbe, C., Schmitt, E., Huls, C., Blankenstein, T. & Diamantstein, T. (1994). Expression of Interleukin-10 in human melanoma. Br J Cancer 70: 1182–1185.

    CAS  Article  Google Scholar 

  • Lopez-Hänninen, E., Kirchner, H. & Atzpodien, J. (1995). Interleukin-2 based home therapy of metastatic renal cell carcinoma: risks and benefits in 215 consecutive single institution patients. J Urol 155(1): 19–25.

    Article  Google Scholar 

  • Matsuda, M., Salazar, F., Petersson, M., Masucci, G., Hansson, J., Pisa, P., Zhang, Q. J., Masucci, M. G. & Kiessling, R. (1994). Interleukin-10 pretreatment protects target cells from tumor- and allo-specific cytotoxic T cells and downregulates HLA class I expression. J Exp Med 180: 2371–2376.

    CAS  Article  Google Scholar 

  • Nakagomi, H., Pisa, P., Pisa, E. K., Yamamoto, Y., Halapi, E., Backlin, K., Juhlin, C. & Kiessling, R. (1995). Lack of interleukin-2 (IL-2) expression and selective expression of IL-10 mRNA in human renal cell carcinoma. Int J Cancer 63: 366–371.

    CAS  Article  Google Scholar 

  • Suzuki, T., Tahara, H., Narula, S., Moore, K. W., Robbins, P. D. & Lotze, M. T. (1995). Viral Interleukin-10 (IL-10), the human herpes virus 4 cellular IL-10 homologue, induces local anergy to allogeneic and syngeneic tumors. J Exp Med 182: 477–486.

    CAS  Article  Google Scholar 

  • Wang, Q., Redovan, C., Tubbs, R., Olencki, T., Klein, E., Kudoh, S., Finke, J. & Bukowski, R. M. (1995). Selective cytokine gene expression in renal cell carcinoma tumor cells and tumor-infiltrating lymphocytes. Int J Cancer 61: 780–785.

    CAS  Article  Google Scholar 

  • Yue, F. Y., Dummer, R., Geertsen, R., Hofbauer, G., Laine, E., Manolio, S. & Burg, G. (1997). Interleukin-10 is a growth factor for human melanoma cells and downregulates HLA class-I, HLA class-II and ICAM molecules. Int J Cancer 71: 630–637.

    CAS  Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

Reprints and Permissions

About this article

Cite this article

Wittke, F., Hoffmann, R., Buer, J. et al. Interleukin 10 (IL-10): an immunosuppressive factor and independent predictor in patients with metastatic renal cell carcinoma. Br J Cancer 79, 1182–1184 (1999). https://doi.org/10.1038/sj.bjc.6690189

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bjc.6690189

Keywords

  • predictors
  • renal cell carcinoma
  • IL-10

Further reading

Search

Quick links