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

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.