Surgery-induced monocytic myeloid-derived suppressor cells expand regulatory T cells in lung cancer
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Jun Wang1,*, Liu Yang2,*, Lu Yu3, Yi-Yin Wang2, Rui Chen2, Jing Qian4, Zhi-Peng Hong5, Xiao-San Su2
1Department of Anesthesiology, The First Affiliated Hospital of Kunming Medical University, Kunming, China
2Biomedical Research Center, The Affiliated Calmette Hospital of Kunming Medical University, Kunming, China
3Department of Pathology, The Affiliated Calmette Hospital of Kunming Medical University, Kunming, China
4Department of Laboratory Medicine, The Affiliated Calmette Hospital of Kunming Medical University, Kunming, China
5Department of Thoracic Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, China
*These authors have contributed equally to this work
Xiao-San Su, email: [email protected]
Keywords: lung cancer, myeloid-derived suppressor cells, regulatory T cells, perioperative period, metastasis
Received: July 25, 2016 Accepted: January 03, 2017 Published: February 02, 2017
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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