Abstract
Abstract Background Interleukin (IL) 17 is secreted by T helper 17 cells and tumor cells. It may induce the proliferation of mesenchymal stem cells (MSCs) in the tumor microenvironment directly and/or via fibroblast growth factor (FGF) and granulocyte-colony stimulating factor (G-CSF) production by tumor-associated macrophages. MSCs play various roles in tumor development and progression, by mediating tumor cell migration, promoting angiogenesis, regulating immune responses, and inducing anti-cancer drug resistance. Therefore, in this study, we examined the association of the IL17/FGF/G-CSF axis with both breast cancer development and response to chemotherapy. Methods Eighty-nine breast cancer patients (34% with luminal, 45% with HER2, and 21% with triple-negative breast cancer) and 55 healthy volunteers were analyzed. Serum IL17, basic FGF, and G-CSF levels were measured using a Luminex system. The primary objective was to evaluate the difference in IL17 serum levels between breast cancer patients and healthy volunteers. Secondary objectives were to determine the correlation of IL17 levels with the basic FGF and G-CSF levels, pathological complete response (pCR) (if neoadjuvant therapy was administered), and disease-free survival (DFS) in breast cancer patients. Statistical analyses were performed using the Mann-Whitney, chi-squared, and log-rank tests. Results Serum levels of IL17 (median, 91.9 vs. 40.3 pg/ml, p<0.0001), basic FGF (median, 63.9 vs. 3.15 pg/ml, p<0.0001), and G-CSF (median, 61.0 vs. 29.4 pg/ml, p<0.0001) were significantly higher in breast cancer patients than in healthy volunteers. IL17 levels were strongly correlated with basic FGF (r=0.86, p<0.0001) and G-CSF (r=0.73, p<0.0001) levels. Among 64 patients who received neoadjuvant therapy, those with low IL17 levels (<91.9 pg/ml) achieved a significantly higher pCR rate than those with high IL17 levels (≥91.9 pg/ml) (56.0% vs. 25.6%, p=0.014). In addition, the DFS at a median follow-up of 35.7 months was significantly higher in patients with low IL17 levels (p=0.0190). Conclusion The IL17/FGF/G-CSF axis was upregulated in breast cancer patients and the levels of these markers were inversely correlated with pCR and prognosis. These results may provide novel insight into the role of IL17 in tumor development and have important implications in the development of IL17 as a target in the treatment of breast tumors. Citation Format: Kawaguchi K, Suzuki E, Yamamoto Y, Saito K, Toi M. Upregulation of the interleukin 17/granulocyte-colony stimulating factor/fibroblast growth factor axis in breast cancer and its negative association with treatment outcome. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-04-22.
Published Version
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