Format

Send to

Choose Destination
Oncotarget. 2017 Mar 7;8(10):17050-17058. doi: 10.18632/oncotarget.14991.

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

Author information

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.

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.

KEYWORDS:

lung cancer; metastasis; myeloid-derived suppressor cells; perioperative period; regulatory T cells

PMID:
28178645
PMCID:
PMC5370021
DOI:
10.18632/oncotarget.14991
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Impact Journals, LLC Icon for PubMed Central
Loading ...
Support Center