title: Tumor-induced myeloid-derived suppressor cells promote tumor progression through oxidative metabolism in human colorectal cancer.
abstract: BACKGROUND
  Expansions of myeloid-derived suppressor cells (MDSCs) have been identified in human solid tumors, including colorectal cancer (CRC). However, the nature of these tumor-associated MDSCs and their interactions with tumor cells in CRC are still poorly understood.
  
  
  METHODS
  The percentages and phenotype of MDSCs in peripheral blood and tumorous and paraneoplastic tissues from CRC patients, as well as the clinical relevance of these MDSCs, were assessed. Age-matched healthy donors were included as controls. The interaction between MDSCs and T cells or tumor cells was investigated in a coculture system in vitro, and the molecular mechanism of the effect of MDSCs on T cells or tumor cells was evaluated.
  
  
  RESULTS
  We discovered that CRC patients had elevated levels of CD33(+)CD11b(+)HLA-DR(-) MDSCs in primary tumor tissues and in peripheral blood, and the elevated circulating MDSCs were correlated with advanced TNM stages and lymph node metastases. Radical resection significantly decreases the proportions of circulating MDSCs and CD4(+)CD25(high)FOXP3(+) regulatory T cells. In vitro, CRC cells mediate the promotion of MDSC induction. Moreover, these tumor-induced MDSCs could suppress T cell proliferation and promote CRC cell growth via cell-to-cell contact. Such effects could be abolished by the inhibition of oxidative metabolism, including the production of nitric oxide (NO), and reactive oxygen species (ROS).
  
  
  CONCLUSIONS
  Our results reveal the functional interdependence between MDSCs, T cells and cancer cells in CRC pathogenesis. Understanding the impact of MDSCs on T cells and tumor cells will be helpful to establish an immunotherapeutic strategy in CRC patients.
authors: State Key Laboratory of Oncology in South China, 651 Dongfeng East Road, Guangzhou, 510060, China. ouyly@sysucc.org.cn.|Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng East Road, Guangzhou, 510060, China. ouyly@sysucc.org.cn.|Intensive Care Unit Department, 651 Dongfeng East Road, Guangzhou, 510060, China. ouyly@sysucc.org.cn.
authors: Li-Ying
authors: LY
authors: OuYang
authors: State Key Laboratory of Oncology in South China, 651 Dongfeng East Road, Guangzhou, 510060, China. wuxj@sysucc.org.cn.|Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng East Road, Guangzhou, 510060, China. wuxj@sysucc.org.cn.|Department of Colorectal Surgery, 651 Dongfeng East Road, Guangzhou, 510060, China. wuxj@sysucc.org.cn.
authors: Xiao-Jun
authors: XJ
authors: Wu
authors: State Key Laboratory of Oncology in South China, 651 Dongfeng East Road, Guangzhou, 510060, China. yeshb@sysucc.org.cn.|Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng East Road, Guangzhou, 510060, China. yeshb@sysucc.org.cn.|Department of Biotherapy, 651 Dongfeng East Road, Guangzhou, 510060, China. yeshb@sysucc.org.cn.
authors: Shu-Biao
authors: SB
authors: Ye
authors: State Key Laboratory of Oncology in South China, 651 Dongfeng East Road, Guangzhou, 510060, China. zhangrx@sysucc.org.cn.|Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng East Road, Guangzhou, 510060, China. zhangrx@sysucc.org.cn.|Department of Colorectal Surgery, 651 Dongfeng East Road, Guangzhou, 510060, China. zhangrx@sysucc.org.cn.
authors: Rong-Xin
authors: RX
authors: Zhang
authors: State Key Laboratory of Oncology in South China, 651 Dongfeng East Road, Guangzhou, 510060, China. lizl@sysucc.org.cn.|Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng East Road, Guangzhou, 510060, China. lizl@sysucc.org.cn.|Department of Biotherapy, 651 Dongfeng East Road, Guangzhou, 510060, China. lizl@sysucc.org.cn.
authors: Ze-Lei
authors: ZL
authors: Li
authors: State Key Laboratory of Oncology in South China, 651 Dongfeng East Road, Guangzhou, 510060, China. liaowei@sysucc.org.cn.|Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng East Road, Guangzhou, 510060, China. liaowei@sysucc.org.cn.|Intensive Care Unit Department, 651 Dongfeng East Road, Guangzhou, 510060, China. liaowei@sysucc.org.cn.
authors: Wei
authors: W
authors: Liao
authors: State Key Laboratory of Oncology in South China, 651 Dongfeng East Road, Guangzhou, 510060, China. panzhzh@sysucc.org.cn.|Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng East Road, Guangzhou, 510060, China. panzhzh@sysucc.org.cn.|Department of Colorectal Surgery, 651 Dongfeng East Road, Guangzhou, 510060, China. panzhzh@sysucc.org.cn.
authors: Zhi-Zhong
authors: ZZ
authors: Pan
authors: State Key Laboratory of Oncology in South China, 651 Dongfeng East Road, Guangzhou, 510060, China. zhenglm@sysucc.org.cn.|Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng East Road, Guangzhou, 510060, China. zhenglm@sysucc.org.cn.|Department of Biotherapy, 651 Dongfeng East Road, Guangzhou, 510060, China. zhenglm@sysucc.org.cn.
authors: Li-Min
authors: LM
authors: Zheng
authors: State Key Laboratory of Oncology in South China, 651 Dongfeng East Road, Guangzhou, 510060, China. zhangxs@sysucc.org.cn.|Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng East Road, Guangzhou, 510060, China. zhangxs@sysucc.org.cn.|Department of Biotherapy, 651 Dongfeng East Road, Guangzhou, 510060, China. zhangxs@sysucc.org.cn.
authors: Xiao-Shi
authors: XS
authors: Zhang
authors: School of Pharmaceutical Sciences, 651 Dongfeng East Road, Guangzhou, 510060, China. wangzh357@mail.sysu.edu.cn.|Center for Cellular and Structural Biology, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China. wangzh357@mail.sysu.edu.cn.
authors: Zhong
authors: Z
authors: Wang
authors: School of Pharmaceutical Sciences, 651 Dongfeng East Road, Guangzhou, 510060, China. liqing66@mail.sysu.edu.cn.|Center for Cellular and Structural Biology, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510060, China. liqing66@mail.sysu.edu.cn.
authors: Qing
authors: Q
authors: Li
authors: State Key Laboratory of Oncology in South China, 651 Dongfeng East Road, Guangzhou, 510060, China. magang@sysucc.org.cn.|Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng East Road, Guangzhou, 510060, China. magang@sysucc.org.cn.|Intensive Care Unit Department, 651 Dongfeng East Road, Guangzhou, 510060, China. magang@sysucc.org.cn.
authors: Gang
authors: G
authors: Ma
authors: State Key Laboratory of Oncology in South China, 651 Dongfeng East Road, Guangzhou, 510060, China. lijiang2@mail.sysu.edu.cn.|Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng East Road, Guangzhou, 510060, China. lijiang2@mail.sysu.edu.cn.|Department of Biotherapy, 651 Dongfeng East Road, Guangzhou, 510060, China. lijiang2@mail.sysu.edu.cn.
authors: Jiang
authors: J
authors: Li
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D018450:Disease Progression; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism*; D009367:Neoplasm Staging; D010084:Oxidation-Reduction; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D015703:Antigens, CD; D006684:HLA-DR Antigens
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