Interleukin (IL) 17 is secreted by T helper 17 cells (Th17) and tumor cells. It may induce the proliferation of mesenchymal stem cells in the tumor microenvironment directly and/or via fibroblast growth factor (FGF) and granulocyte-colony stimulating factor (G-CSF) production by tumor-associated macrophages. Indoleamine 2,3-dioxygenase (IDO) mediates a protolerogenic mechanism that suppresses T cells including TH17, providing balance or feedback control in immune reactions. However, little is known about IL17/FGF/G-CSF axis and its correlation with IDO-1 and 2 in breast cancer. Therefore, in this study, we examined the association of the IL17/FGF/G-CSF axis and IDO-1 and 2 with both breast cancer development and clinical outcome.
Eighty-nine breast cancer patients 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), and disease-free survival (DFS) in breast cancer patients.
Serum level of IL17 (median, 91.9 vs. 40.3 pg/ml, p < 0.0001) was 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, high IL17 level was correlated with high IDO-2 expression (p = 0.046).
The IL17/FGF/G-CSF axis and IDO-2 expression were 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 and IDO-2 in tumor development and have important implications in the development of IL17 and IDO-2 as a target in the treatment of breast tumors.
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All authors have declared no conflicts of interest.