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

J Wang, L Yang, L Yu, YY Wang, R Chen, J Qian… - Oncotarget, 2017 - ncbi.nlm.nih.gov
J Wang, L Yang, L Yu, YY Wang, R Chen, J Qian, ZP Hong, XS Su
Oncotarget, 2017ncbi.nlm.nih.gov
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 …
Abstract
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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