| First Author | Novitskiy SV | Year | 2011 |
| Journal | Cancer Discov | Volume | 1 |
| Issue | 5 | Pages | 430-41 |
| PubMed ID | 22408746 | Mgi Jnum | J:185747 |
| Mgi Id | MGI:5429810 | Doi | 10.1158/2159-8290.CD-11-0100 |
| Citation | Novitskiy SV, et al. (2011) TGF-beta receptor II loss promotes mammary carcinoma progression by Th17 dependent mechanisms. Cancer Discov 1(5):430-41 |
| abstractText | We report that IL-17 significantly increases the secretion of CXCL1 and CXCL5 from mammary carcinoma cells, which is downregulated by TGF-beta through the type II TGF-beta receptor (TbetaRII). Carcinoma cells with conditional knockout of TbetaRII (Tgfbr2(KO)) have enhanced sensitivity to IL-17a in the stimulation of chemokine secretion. During polyoma middle T (PyMT) induced tumor progression, levels of Th17 inducing cytokines TGF-beta, IL-6, IL-23 were increased in PyMT/Tgfbr2(KO) tumors, which was associated with an increased number of Th17 cells. IL-17 increased the suppressive function of MDSCs on T cells through the upregulation of Arg, IDO, and COX2. Treatment of PyMT/Tgfbr2(KO) mice with anti-IL-17 Ab decreased carcinoma growth and metastatic burden. Analysis of human breast cancer transcriptome databases showed a strong association between IL-17 gene expression and poor outcome in lymph node positive, estrogen receptor negative or luminal B subtypes suggesting potential therapeutic approaches. |
