Tumor-induced myeloid-derived suppressor cells promote tumor progression through oxidative metabolism in human colorectal cancer

Journal of Translational Medicine

Jiang Li⁴  Gang Ma²  Qing Li³  Zhong Wang³  Xiao-Shi Zhang⁴  Li-Min Zheng⁴  Zhi-Zhong Pan¹  Wei Liao²  Ze-Lei Li⁴  Rong-xin Zhang¹  Shu-Biao Ye⁴  Xiao-Jun Wu¹  Li-Ying OuYang² 

[1] Department of Colorectal Surgery, 651 Dongfeng East Road, Guangzhou 510060, China;Intensive Care Unit Department, 651 Dongfeng East Road, Guangzhou 510060, China;Center for Cellular and Structural Biology, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, China;Department of Biotherapy, 651 Dongfeng East Road, Guangzhou 510060, China

关键词: Radical resection;    Colorectal carcinoma;    Myeloid-derived suppressor cells;   

Others  :  1137650
DOI  :  10.1186/s12967-015-0410-7

 received in 2014-05-14, accepted in 2015-01-17,  发布年份 2015

【 摘 要 】

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^highFOXP3⁺ 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.

【 授权许可】

   
2015 Ouyang et al.; licensee BioMed Central.

【 图 表 】

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