Myeloid-derived suppressor cells inhibit T cell proliferation in human extranodal NK/T cell lymphoma: a novel prognostic indicator.
The expansion of myeloid-derived suppressor cells (MDSCs) and its correlation with advanced disease stage have been shown in solid cancers. Here, we investigated the functional features and clinical significance of MDSCs in extranodal NK/T cell lymphoma (ENKL). A higher percentage of circulating HLA-DR(-)CD33(+)CD11b(+) MDSCs was observed in ENKL patients than in healthy controls (P < 0.05, n = 32) by flow cytometry analysis. These MDSCs from ENKL patients (ENKL-MDSCs) consisted of CD14(+) monocytic (Mo-MDSCs, >60 %) and CD15(+) granulocytic (PMN-MDSCs, <20 %) MDSCs. Furthermore, these ENKL-MDSCs expressed higher levels of Arg-1, iNOS and IL-17 compared to the levels of MDSCs from healthy donors, and they expressed moderate levels of TGFβ and IL-10 but lower levels of CD66b. The ENKL-MDSCs strongly suppressed the anti-CD3-induced allogeneic and autologous CD4 T cell proliferation (P < 0.05), but they only slightly suppressed CD8 T cell proliferation (P > 0.05). Interestingly, ENKL-MDSCs inhibited the secretion of IFNγ but promoted IL-10, IL-17 and TGFβ secretion as well as Foxp3 expression in T cells. The administration of inhibitors of iNOS, Arg-1 and ROS significantly reversed the suppression of anti-CD3-induced T cell proliferation by MDSCs (P < 0.05). Importantly, based on multivariate Cox regression analysis, the HLA-DR(-)CD33(+)CD11b(+) cells and CD14(+) Mo-MDSCs were independent predictors for disease-free survival (DFS, P = 0.013 and 0.016) and overall survival (OS, P = 0.017 and 0.027). Overall, our results identified for the first time that ENKL-MDSCs (mainly Mo-MDSCs) have a prognostic value for patients and a suppressive function on T cell proliferation.
State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.|Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.|Department of Biotherapy, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.
Han
H
Zhang
State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.|Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.|Department of Biotherapy, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.
Ze-Lei
ZL
Li
State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.|Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.|Department of Biotherapy, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.
Shu-Biao
SB
Ye
State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.|Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.|Intensive Care Unit Department, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.
Li-Ying
LY
Ouyang
State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.|Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.|Department of Radiotherapy, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.
Yu-Shan
YS
Chen
State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.|Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.|Department of Biotherapy, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.
Jia
J
He
State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.|Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.|Department of Medical Oncology, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.
Hui-Qiang
HQ
Huang
State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.|Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China.
Yi-Xin
YX
Zeng
State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China. zhangxsh@sysucc.org.cn.|Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China. zhangxsh@sysucc.org.cn.|Department of Biotherapy, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China. zhangxsh@sysucc.org.cn.
Xiao-Shi
XS
Zhang
State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China. lijiang2@mail.sysu.edu.cn.|Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China. lijiang2@mail.sysu.edu.cn.|Department of Biotherapy, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China. lijiang2@mail.sysu.edu.cn.
Jiang
J
Li
D000111:Acetylcysteine / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D054391:Lymphoma, Extranodal NK-T-Cell / Q000175:diagnosis / Q000276:immunology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors; D055815:Young Adult; D019323:omega-N-Methylarginine / Q000494:pharmacology
D016207:Cytokines; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; C404735:N(omega)-hydroxynorarginine; D017382:Reactive Oxygen Species; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D000111:Acetylcysteine
Hematopoietic malignancy; Immunosuppression; MDSCs; NK/T cell lymphoma; Prognosis