Research Papers:
Tumor-infiltrating macrophages express interleukin-25 and predict a favorable prognosis in patients with gastric cancer after radical resection
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Abstract
Jinqing Li1, Yuan Liao1,2, Tong Ding3, Bo Wang4, Xingjuan Yu1, Yifan Chu1, Jing Xu1, Limin Zheng1,5
1Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China
2Department of Laboratory Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, P.R. China
3Department of Cell Biology, Nanjing Medical University, Nanjing, P.R. China
4Department of Urology, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, P.R. China
5Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, P.R. China
Correspondence to:
Limin Zheng, e-mail: [email protected]
Keywords: interleukin-25, macrophages, transforming growth factor-β1, gastric cancer
Received: August 20, 2015 Accepted: January 17, 2016 Published: January 31, 2016
ABSTRACT
Interleukin-25 (IL-25) is a recently identified member of the proinflammatory IL-17 cytokine family; however, its role in human tumors remains largely unknown. The aim of this study was to investigate the cellular source and clinical significance of IL-25 in gastric cancer (GC) in situ. The results demonstrated that macrophages (Mφs) were the primary IL-25-expressing cells (IL-25+) in GC in situ. Moreover, IL-25+ cells were highly enriched in the intra-tumoral (IT) region of GC tissues (p < 0.001). The production of IL-25 in Mφs exposed to culture supernatant from gastric cancer cell line SGC7901 in vitro was induced by transforming growth factor-β1, and their density in the IT region was positively associated with those of other effector immune cells, namely, CD4+ T cells, CD8+ T cells and CD103+T cells (p < 0.01). This suggested that macrophages might produce IL-25 to create an antitumor micromilieu in GC tissues. The level of IL-25+IT cells was positively associated with histological grade (p < 0.001) and found to be an independent predictor of favorable survival (p = 0.024) in patients with GC after radical resection. These findings suggest that IL-25+IT cells may be a novel therapeutic target in those patients.
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