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

Autor: Lu Yu, Xiaosan Su, Yiyin Wang, Rui Chen, Jing Qian, Jun Wang, Zhi-Peng Hong, Liu Yang
Rok vydání: 2017
Předmět:
0301 basic medicine
medicine.medical_specialty
Lung Neoplasms
Time Factors
CD14
perioperative period
CD33
chemical and pharmacologic phenomena
Cell Count
Kaplan-Meier Estimate
T-Lymphocytes
Regulatory
Monocytes
regulatory T cells
Metastasis
Carcinoma
Lewis Lung
03 medical and health sciences
0302 clinical medicine
Cell Line
Tumor
medicine
Animals
Humans
metastasis
Prospective Studies
Neoplasm Metastasis
Lung cancer
Lung
Arginase
Reverse Transcriptase Polymerase Chain Reaction
business.industry
Myeloid-Derived Suppressor Cells
FOXP3
hemic and immune systems
Forkhead Transcription Factors
Perioperative
Flow Cytometry
medicine.disease
Surgery
Gene Expression Regulation
Neoplastic
Mice
Inbred C57BL
lung cancer
030104 developmental biology
medicine.anatomical_structure
Oncology
030220 oncology & carcinogenesis
Myeloid-derived Suppressor Cell
business
Research Paper
Zdroj: Oncotarget
ISSN: 1949-2553
DOI: 10.18632/oncotarget.14991
Popis: // Jun Wang 1, * , Liu Yang 2, * , Lu Yu 3 , Yi-Yin Wang 2 , Rui Chen 2 , Jing Qian 4 , Zhi-Peng Hong 5 , Xiao-San Su 2 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 * These authors have contributed equally to this work Correspondence to: Xiao-San Su, email: suxs163@163.com 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 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.
Databáze: OpenAIRE
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