Tumor-infiltrating macrophages express interleukin-25 and predict a favorable prognosis in patients with gastric cancer after radical resection

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// Jinqing Li 1 , Yuan Liao 1, 2 , Tong Ding 3 , Bo Wang 4 , Xingjuan Yu 1 , Yifan Chu 1 , Jing Xu 1 , Limin Zheng 1, 5 1 Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, P.R. China 2 Department of Laboratory Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, P.R. China 3 Department of Cell Biology, Nanjing Medical University, Nanjing, P.R. China 4 Department 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 5 Key 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: zhenglm@mail.sysu.edu.cn 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.