IL-17 inhibits the accumulation of myeloid-derived suppressor cells in breast cancer via activating STAT3

被引:36
作者
Ma, Min [1 ]
Huang, Wei [1 ]
Kong, Dehua [1 ]
机构
[1] Nanjing Gaochun Peoples Hosp, Dept Clin Lab, Nanjing, Jiangsu, Peoples R China
关键词
MDSC; IL-17; Breast Cancer; STAT3; TH17; CELLS; INTERLEUKIN-17; INFLAMMATION; IMMUNITY;
D O I
10.1016/j.intimp.2018.04.013
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Breast cancer (BC) is one of the most common cancers, with high recurrence rate and poor prognosis of recurrent metastatic disease. In our study, we analyzed the markers and development of markers of myeloid-derived suppressor cells (MDSCs) for BC progression and occurrence. MDSCs is one of the major orchestrators of the immunosuppressive network, are associated with immune suppression and considered a prime target for cancer immunotherapy. Interleukin-17 (IL-17) is a signature cytokine of Th17 cells. Previous research has indicated that IL-17 plays a proinflammatory role. It was found to increase frequencies at certain tumors and involved in angiogenesis. This study aims to elucidate the biological role of IL-17 on MDSC in BC cells. Expression of MDSC in peripheral blood of 80 BCE patients and 20 healthy volunteers was compared. Our results indicate that MDSC numbers in patients with BC were higher than healthy donors. Moreover, the clinical grade and prognosis were correlate with the number of MDSC. In this study, we investigated the effect of IL-17 on MDSCs. CCK-8 assay and flow cytometry were used to assess the proliferation and apoptosis of cells. The expression of key MDSC-related molecules was detected by western blotting. We identified administration with IL-17 in vitro significantly induced MDSC differentiation, inhibited their proliferation and triggered apoptosis. In addition, Low IL-17 inhibited the activation of STAT3, leading to increase formation of MDSCs in BC. Our results from experiments suggest that the effects of IL-17 mediate activation of STAT3 signaling in BC cells. Taken together, our study shows that MDSCs can be a new type prognostic marker in BC patient. Targeting IL-17/Stat3 signaling may be a promising strategy for BC treatment.
引用
收藏
页码:148 / 156
页数:9
相关论文
共 33 条
[1]   Doxorubicin Eliminates Myeloid-Derived Suppressor Cells and Enhances the Efficacy of Adoptive T-Cell Transfer in Breast Cancer [J].
Alizadeh, Darya ;
Trad, Malika ;
Hanke, Neale T. ;
Larmonier, Claire B. ;
Janikashvili, Nona ;
Bonnotte, Bernard ;
Katsanis, Emmanuel ;
Larmonier, Nicolas .
CANCER RESEARCH, 2014, 74 (01) :104-118
[2]   Tumor-Derived Granulocyte-Macrophage Colony-Stimulating Factor Regulates Myeloid Inflammation and T Cell Immunity in Pancreatic Cancer [J].
Bayne, Lauren J. ;
Beatty, Gregory L. ;
Jhala, Nirag ;
Clark, Carolyn E. ;
Rhim, Andrew D. ;
Stanger, Ben Z. ;
Vonderheide, Robert H. .
CANCER CELL, 2012, 21 (06) :822-835
[3]   Interleukin-17 inhibits tumor cell growth by means of a T-cell-dependent mechanism [J].
Benchetrit, F ;
Ciree, A ;
Vives, V ;
Warnier, G ;
Gey, A ;
Sautès-Fridman, C ;
Fossiez, F ;
Haicheur, N ;
Fridman, WH ;
Tartour, E .
BLOOD, 2002, 99 (06) :2114-2121
[4]   Breathing new life into immunotherapy: review of melanoma, lung and kidney cancer [J].
Drake, Charles G. ;
Lipson, Evan J. ;
Brahmer, Julie R. .
NATURE REVIEWS CLINICAL ONCOLOGY, 2014, 11 (01) :24-37
[5]   Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012 [J].
Ferlay, Jacques ;
Soerjomataram, Isabelle ;
Dikshit, Rajesh ;
Eser, Sultan ;
Mathers, Colin ;
Rebelo, Marise ;
Parkin, Donald Maxwell ;
Forman, David ;
Bray, Freddie .
INTERNATIONAL JOURNAL OF CANCER, 2015, 136 (05) :E359-E386
[6]   Elevated myeloid-derived suppressor cells in pancreatic, esophageal and gastric cancer are an independent prognostic factor and are associated with significant elevation of the Th2 cytokine interleukin-13 [J].
Gabitass, Rachel F. ;
Annels, Nicola E. ;
Stocken, Deborah D. ;
Pandha, Hardev A. ;
Middleton, Gary W. .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2011, 60 (10) :1419-1430
[7]   Myeloid-derived suppressor cells as regulators of the immune system [J].
Gabrilovich, Dmitry I. ;
Nagaraj, Srinivas .
NATURE REVIEWS IMMUNOLOGY, 2009, 9 (03) :162-174
[8]   Leptin as a mediator of tumor-stromal interactions promotes breast cancer stem cell activity [J].
Giordano, Cinzia ;
Chemi, Francesca ;
Panza, Salvatore ;
Barone, Ines ;
Bonofiglio, Daniela ;
Lanzino, Marilena ;
Cordella, Angela ;
Campana, Antonella ;
Hashim, Adnan ;
Rizza, Pietro ;
Leggio, Antonella ;
Gyorffy, Balazs ;
Simoes, Bruno M. ;
Clarke, Robert B. ;
Weisz, Alessandro ;
Catalano, Stefania ;
Ando, Sebastiano .
ONCOTARGET, 2016, 7 (02) :1262-1275
[9]   IL-17 family: Cytokines, receptors and signaling [J].
Gu, Chunfang ;
Wu, Ling ;
Li, Xiaoxia .
CYTOKINE, 2013, 64 (02) :477-485
[10]   IL-17 induces AKT-dependent IL-6/JAK2/STAT3 activation and tumor progression in hepatocellular carcinoma [J].
Gu, Fang-Ming ;
Li, Quan-Lin ;
Gao, Qiang ;
Jiang, Jia-Hao ;
Zhu, Kai ;
Huang, Xiao-Yong ;
Pan, Jin-Feng ;
Yan, Jun ;
Hu, Jin-Hui ;
Wang, Zheng ;
Dai, Zhi ;
Fan, Jia ;
Zhou, Jian .
MOLECULAR CANCER, 2011, 10