机构:[1]Department of Anesthesiology, The First Affiliated Hospital of Kunming Medical University, Kunming, China外科科室麻醉手术科(医技)昆明医科大学附属第一医院[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外科科室胸外科昆明医科大学附属第一医院
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.
基金:
National Natural Science Foundation of China (NSFC)National Natural Science Foundation of China [31360223]