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Introduction: Interleukin 17 (IL-17), correlating with advanced stage or poor prognosis of cancer patients, appears to contribute to tumor progression. Here we demonstrated the presence of IL-17 receptor A (IL-17RA) on the tumor cells directly promoting tumor growth, angiogenesis and metastasis. Methods: B16F10 and its derived IL-17RA deficient melanoma cells were stimulated with recombinant IL-17 (γmIL-17) or subcutaneously implanted into C57BL/6 mice. Cell proliferation, cell invasion, tumor growth, metastasis and angiogensis were monitored and anti-tumor immunity was also assessed. Results: As compared with those in the control B16F10 cells, the γmIL-17 inducing cell proliferation, migration and invasion were significantly reduced in the derived IL-17RA-deficient cells. The tumor growth and metastasis were also apparently reduced in the mice bearing the IL-17RA deficient tumors. In fact, not ony the expression of MMP2 and MMP9 but also the production of VEGF and HGF were reduced both in vitro and in vivo. Additionally, the increased levels of IFNγ+ and Granzyme B+ immune cells as well as the reduced numbers of Tregs and MDSCs appeared in the mice bearing the IL-17RA deficient tumors, indicating the lack of IL-17 enhancing the CTL activity and other anti-tumor immunity. Conclusion: These findings support the hypothesis that IL-17/IL-17RA signaling directly promotes tumor growth as well as recruits MDSCs and Treg cells, resulting in tumor progression. It suggests IL-17RA on tumors as a potential therapeutic target for cancer therapy. Citation Format: Ya-Shan Chen, Chao-Lin Liu, Hui-Shan Chen, Su-Ting Wu, Chia-Rui Shen. Decreased tumor progression by the knockdown of interleukin 17 receoptor A in the B16F10 melanoma model. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 442. doi:10.1158/1538-7445.AM2015-442