Roles of inflammatory cytokines in the progression of gastric cancer: friends or foes?

Increasing evidence is being reported regarding the hypothesis that several proinflammatory and anti-inflammatory cytokines may promote tumor progression and affect the host antitumor response. However, the manner in which a local cytokine network operates in tumor development remains unclear. We reviewed the literature to examine the consequences of novel insights into inflammatory cytokines associated with gastric cancer progression. The Medline and EMBASE databases were searched for publications regarding the role of inflammatory cytokines in the development of gastric cancer. A number of studies have suggested that several proinflammatory and anti-inflammatory cytokines promote tumor progression through the direct activation of nuclear factor-κB (NF-κB) and the upregulation of angiogenesis and adhesion molecules. Furthermore, these processes suppress host antitumor immunity, leading to tumor progression and metastasis. In patients with advanced gastric cancer, most cytokines that enhance or suppress host antitumor immunity appear to have elevated serum and local expression levels. The net cytokine environment fluctuates at various stages of tumor development. In conclusion, a more detailed understanding of the differential roles of malignant cell-derived and hostderived cytokines at different stages of the malignant process could, consequently, open new avenues for the manipulation of cytokine expression and function in cancer immunotherapy for gastric cancer.