IL-17 can promote tumor growth through an IL-6-Stat3 signaling pathway

Although the Th17 subset and its signature cytokine, interleukin (IL)-17A (IL-17), are implicated in certain autoimmune diseases, their role in cancer remains to be further explored. IL-17 has been shown to be elevated in several types of cancer, but how it might contribute to tumor growth is still...

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Bibliographic Details
Published in:The Journal of experimental medicine 2009-07, Vol.206 (7), p.1457-1464
Main Authors: Wang, Lin, Yi, Tangsheng, Kortylewski, Marcin, Pardoll, Drew M, Zeng, Defu, Yu, Hua
Format: Article
Language:English
Subjects:
Adoptive Transfer
Animals
Brief Definitive Report
CD4-Positive T-Lymphocytes - cytology
CD4-Positive T-Lymphocytes - immunology
Cell Line, Tumor
Humans
Interferon-gamma - genetics
Interferon-gamma - immunology
Interleukin-17 - genetics
Interleukin-17 - immunology
Interleukin-6 - genetics
Interleukin-6 - immunology
Mice
Mice, Inbred C57BL
Mice, Knockout
Neoplasms - immunology
Neoplasms - pathology
Signal Transduction - immunology
STAT3 Transcription Factor - genetics
STAT3 Transcription Factor - immunology
Stromal Cells - cytology
Stromal Cells - immunology
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Summary:Although the Th17 subset and its signature cytokine, interleukin (IL)-17A (IL-17), are implicated in certain autoimmune diseases, their role in cancer remains to be further explored. IL-17 has been shown to be elevated in several types of cancer, but how it might contribute to tumor growth is still unclear. We show that growth of B16 melanoma and MB49 bladder carcinoma is reduced in IL-17(-/-) mice but drastically accelerated in IFN-gamma(-/-) mice, contributed to by elevated intratumoral IL-17, indicating a role of IL-17 in promoting tumor growth. Adoptive transfer studies and analysis of the tumor microenvironment suggest that CD4(+) T cells are the predominant source of IL-17. Enhancement of tumor growth by IL-17 involves direct effects on tumor cells and tumor-associated stromal cells, which bear IL-17 receptors. IL-17 induces IL-6 production, which in turn activates oncogenic signal transducer and activator of transcription (Stat) 3, up-regulating prosurvival and proangiogenic genes. The Th17 response can thus promote tumor growth, in part via an IL-6-Stat3 pathway.
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.20090207