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¹ Department of Cancer Immunotherapeutics and Tumor Immunology, ² Department of Hematology and Hematopoietic Cell Transplantation, ³ Department of Diabetes and Metabolic Diseases Research, and ⁴ Graduate School of Biological Science, Beckman Research Institute at City of Hope Medical Center, Duarte, CA 91010
⁵ Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21231

CORRESPONDENCE H. Yu: hyu{at}coh.org OR D. Zeng: dzeng{at}coh.org OR D. Pardoll: dmpardol{at}jhmi.edu

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-^–/– 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.

Abbreviations used: MEF, mouse embryonic fibroblast; phospho-Stat3, phosphorylated Stat3.

© 2009 Wang et al.
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