Abstract
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. © 1999 Cancer Research Campaign
Keywords: predictors, renal cell carcinoma, IL-10
Full Text
The Full Text of this article is available as a PDF (72.4 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Atzpodien J., Lopez Hänninen E., Kirchner H., Bodenstein H., Pfreundschuh M., Rebmann U., Metzner B., Illiger H. J., Jakse G., Niesel T. Multiinstitutional home-therapy trial of recombinant human interleukin-2 and interferon alfa-2 in progressive metastatic renal cell carcinoma. J Clin Oncol. 1995 Feb;13(2):497–501. doi: 10.1200/JCO.1995.13.2.497. [DOI] [PubMed] [Google Scholar]
- Blay J. Y., Burdin N., Rousset F., Lenoir G., Biron P., Philip T., Banchereau J., Favrot M. C. Serum interleukin-10 in non-Hodgkin's lymphoma: a prognostic factor. Blood. 1993 Oct 1;82(7):2169–2174. [PubMed] [Google Scholar]
- Buelens C., Verhasselt V., De Groote D., Thielemans K., Goldman M., Willems F. 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. 1997 Mar;27(3):756–762. doi: 10.1002/eji.1830270326. [DOI] [PubMed] [Google Scholar]
- Ding L., Linsley P. S., Huang L. Y., Germain R. N., Shevach E. M. IL-10 inhibits macrophage costimulatory activity by selectively inhibiting the up-regulation of B7 expression. J Immunol. 1993 Aug 1;151(3):1224–1234. [PubMed] [Google Scholar]
- Dummer W., Bastian B. C., Ernst N., Schänzle C., Schwaaf A., Bröcker E. B. Interleukin-10 production in malignant melanoma: preferential detection of IL-10-secreting tumor cells in metastatic lesions. Int J Cancer. 1996 May 29;66(5):607–610. doi: 10.1002/(SICI)1097-0215(19960529)66:5<607::AID-IJC4>3.0.CO;2-X. [DOI] [PubMed] [Google Scholar]
- Fiorentino D. F., Bond M. W., Mosmann T. R. Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med. 1989 Dec 1;170(6):2081–2095. doi: 10.1084/jem.170.6.2081. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Krüger-Krasagakes S., Krasagakis K., Garbe C., Schmitt E., Hüls C., Blankenstein T., Diamantstein T. Expression of interleukin 10 in human melanoma. Br J Cancer. 1994 Dec;70(6):1182–1185. doi: 10.1038/bjc.1994.469. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Matsuda M., Salazar F., Petersson M., Masucci G., Hansson J., Pisa P., Zhang Q. J., Masucci M. G., Kiessling R. Interleukin 10 pretreatment protects target cells from tumor- and allo-specific cytotoxic T cells and downregulates HLA class I expression. J Exp Med. 1994 Dec 1;180(6):2371–2376. doi: 10.1084/jem.180.6.2371. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nakagomi H., Pisa P., Pisa E. K., Yamamoto Y., Halapi E., Backlin K., Juhlin C., Kiessling R. Lack of interleukin-2 (IL-2) expression and selective expression of IL-10 mRNA in human renal cell carcinoma. Int J Cancer. 1995 Nov 3;63(3):366–371. doi: 10.1002/ijc.2910630311. [DOI] [PubMed] [Google Scholar]
- Suzuki T., Tahara H., Narula S., Moore K. W., Robbins P. D., Lotze M. T. 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. 1995 Aug 1;182(2):477–486. doi: 10.1084/jem.182.2.477. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wang Q., Redovan C., Tubbs R., Olencki T., Klein E., Kudoh S., Finke J., Bukowski R. M. Selective cytokine gene expression in renal cell carcinoma tumor cells and tumor-infiltrating lymphocytes. Int J Cancer. 1995 Jun 9;61(6):780–785. doi: 10.1002/ijc.2910610607. [DOI] [PubMed] [Google Scholar]
- Yue F. Y., Dummer R., Geertsen R., Hofbauer G., Laine E., Manolio S., Burg G. Interleukin-10 is a growth factor for human melanoma cells and down-regulates HLA class-I, HLA class-II and ICAM-1 molecules. Int J Cancer. 1997 May 16;71(4):630–637. doi: 10.1002/(sici)1097-0215(19970516)71:4<630::aid-ijc20>3.0.co;2-e. [DOI] [PubMed] [Google Scholar]
- de Waal Malefyt R., Haanen J., Spits H., Roncarolo M. G., te Velde A., Figdor C., Johnson K., Kastelein R., Yssel H., de Vries J. E. Interleukin 10 (IL-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. 1991 Oct 1;174(4):915–924. doi: 10.1084/jem.174.4.915. [DOI] [PMC free article] [PubMed] [Google Scholar]
- de Waal Malefyt R., Yssel H., de Vries J. E. Direct effects of IL-10 on subsets of human CD4+ T cell clones and resting T cells. Specific inhibition of IL-2 production and proliferation. J Immunol. 1993 Jun 1;150(11):4754–4765. [PubMed] [Google Scholar]