Surgery-induced monocytic myeloid-derived suppressor cells expand regulatory T cells in lung cancer.
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.
Department of Anesthesiology, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
Jun
J
Wang
Biomedical Research Center, The Affiliated Calmette Hospital of Kunming Medical University, Kunming, China.
Liu
L
Yang
Department of Pathology, The Affiliated Calmette Hospital of Kunming Medical University, Kunming, China.
Lu
L
Yu
Biomedical Research Center, The Affiliated Calmette Hospital of Kunming Medical University, Kunming, China.
Yi-Yin
YY
Wang
Biomedical Research Center, The Affiliated Calmette Hospital of Kunming Medical University, Kunming, China.
Rui
R
Chen
Department of Laboratory Medicine, The Affiliated Calmette Hospital of Kunming Medical University, Kunming, China.
Jing
J
Qian
Department of Thoracic Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
Zhi-Peng
ZP
Hong
Biomedical Research Center, The Affiliated Calmette Hospital of Kunming Medical University, Kunming, China.
Xiao-San
XS
Su
D000818:Animals; D001119:Arginase / Q000276:immunology / Q000378:metabolism; D018827:Carcinoma, Lewis Lung / Q000235:genetics / Q000276:immunology / Q000601:surgery; D002452:Cell Count; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000601:surgery; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology* / Q000601:surgery; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D000072737:Myeloid-Derived Suppressor Cells / Q000276:immunology* / Q000378:metabolism; D009362:Neoplasm Metastasis; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D001119:Arginase
lung cancer; metastasis; myeloid-derived suppressor cells; perioperative period; regulatory T cells