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Surgery-induced monocytic myeloid-derived suppressor cells expand regulatory T cells in lung cancer

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机构: [1]Department of Anesthesiology, The First Affiliated Hospital of Kunming Medical University, Kunming, China [2]Biomedical Research Center, The Affiliated Calmette Hospital of Kunming Medical University, Kunming, China [3]Department of Pathology, The Affiliated Calmette Hospital of Kunming Medical University, Kunming, China [4]Department of Laboratory Medicine, The Affiliated Calmette Hospital of Kunming Medical University, Kunming, China [5]Department of Thoracic Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, China
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关键词: lung cancer myeloid-derived suppressor cells regulatory T cells perioperative period metastasis

摘要:
While monocytic myeloid-derived suppressor cells (M-MDSCs) have been reported to induce the development of regulatory T cells (Treg), little is known about their correlation with Treg during perioperative period. Here, we demonstrated that the M-MDSCs expressing CD11b(+)CD33(+)HLA-DR-CD14(+) in lung cancer patients after thoractomy significantly increased in comparison with preoperation, and their accumulation linearly correlated with an increase in Treg. Surgery-induced M-MDSCs, in addition to have high arginase activity, were more efficient in suppressing T-cell proliferation. Furthermore, the surgery-induced Treg expressed high levels of Foxp3, PD-1 and CTLA-4. Surgery-induced M-MDSCs were more potent in expending Treg when cocultured with autologous T cells in vitro. Using a lung metastasis mouse model, we demonstrated that the M-MDSCs at postoperative period were significantly increased and linearly correlated with Treg. We also showed that all-trans retinoic acid significantly inhibited the induction and proliferation of M-MDSCs, suppressed expansion of Treg, and finally prevented tumor metastasis in the mice after tumor resection. Receiver operating characteristic analyses revealed the superiority of surgery-induced M-MDSCs and Treg to those at preoperative period as a prognostic marker for lung cancer patients. Taken together, our results link the presence of surgery-induced M-MDSCs with the emergence of Treg and identify M-MDSCs and Treg derived postoperatively as potential indicators of tumor metastasis.

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影响因子: 最新[2023版] 最新五年平均 出版当年[2017版] 出版当年五年平均 出版前一年[2016版]

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第一作者机构: [1]Department of Anesthesiology, The First Affiliated Hospital of Kunming Medical University, Kunming, China
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