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. 2017 Dec 15;8:1840. doi: 10.3389/fimmu.2017.01840

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Copyright © 2017 Jiang, Chen, Zhang, Zhang, Ye, Liu, Yu, Wei, Ren and Yu.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Tumor-derived interleukin-6 (IL-6) is significantly correlated with the number of infiltrated myeloid-derived suppressor cells (MDSCs) in situ both at the mRNA and protein levels. (A) The expression of the IL-6 protein and CD33⁺ MDSCs infiltration in 253 paraffin-embedded breast tissues from cohort 1 and cohort 2 was studied by immunohistochemistry (IHC). We found greater MDSCs infiltration in cancer tissues with a high level of IL-6. (B) The correlation between the expression of IL-6 and MDSCs was compared both in cohort 1 and cohort 2 in situ (n = 253). The average number of MDSCs in the IL-6^low group was significantly lower than that in the IL-6^high group in both cohorts 1 and 2. Pearson correlation analysis revealed a positive correlation between the expression of IL-6 and the number of MDSCs in situ in both cohorts. (C) The infiltration percentage of the CD45⁺CD33⁺CD13⁺CD14⁻CD15⁻ subpopulation in 20 fresh breast cancer tissue samples was detected using flow cytometry. (1) The subpopulation was gated using anti-CD45 mAb and isotype control was used; (2) The CD45⁺CD33⁺CD13⁺CD14⁻CD15⁻ subpopulation in adjacent normal tissues. (3) The proportion of the interested subpopulation significantly increased in cancer tissues. (D) Based on the median relative RNA level of IL-6, breast cancer samples were divided into IL-6^high and IL-6^low groups. The average IL-6 mRNA level in the IL-6^high group was 37.25-fold higher than that in the IL-6^low group (P = 0.0093) (n = 20). (E) A higher frequency of MDSCs was detected in the IL-6^high group compared to in the IL-6^low group. (F) A correlation analysis on MDSCs number and IL-6 level was carried out (R² = 0.4399, P = 0.0014) (n = 20). *P < 0.05, **P < 0.01, ***P < 0.001.