Natural compounds that regulate lymph node sinus macrophages: Inducing an anti-tumor effect by regulating macrophage activation

Recent progress in anti-tumor therapy has revealed the significance of anti-tumor immune responses in tumor progression and clinical course in several kinds of malignant tumors. The draining lymph node is an important immune system component that contains a number of antigen-presenting cells, which induce rapid immune responses to foreign antigens. Current studies have shown that higher expression of CD169 on lymph node sinus macrophages is associated with the induction of anti-tumor immunity. In the present study, we searched for natural compounds that regulate the CD169-positive phenotype in macrophages to identify potential new anti-cancer agents targeting macrophage activation. Among 50 natural compounds, aculeatiside A, naringin, and onionin A significantly induced the CD169-positive phenotype in human monocyte-derived macrophages. These compounds also induced CD169 overexpression and secretion of inflammatory cytokines, including interleukin (IL)-1 beta and IL-12, in murine macrophages. Subcutaneous injection of aculeatiside A and naringin enhanced mRNA expression of IL-1 beta, IL12, and CD169 in regional lymph nodes in mice. These findings suggest aculeatiside A and naringin may enhance antitumor immune responses by inducing CD169-positive macrophages in lymph nodes.