The Role of IL-31 in Tumorigenesis

The development of new drugs against cancer has been a great challenge in recent years. While most of the drugs are designed to kill tumor cells, a growing body of literature suggests that the modulation of host cells e.g., the immune system against tumor cells may also act as a potential target for therapy. Based on a screening technique in which we identified host factors which are upregulated in the plasma following chemotherapy, we identified IL-31 as a possible factor with immune modulation properties. IL-31 has been shown to promote an acute immune response by activating macrophages and T-cytotoxic cells leading to dermatitis in mouse and human. However, the role of IL-31 in tumorigenesis is not known. Here we generated a construct of IL-31 fused with a stable protein (IL-31-IgG) in order to maintain high levels of IL-31 in the blood. IL-31-IgG directly inhibits the proliferation and viability of tumor cells which express the receptors for IL-31. Consequently, mice bearing 4T1 or MC-38, murine breast and colon carcinomas, respectively, that have been treated with IL-31-IgG resulted in reduced tumor growth, inhibition of angiogenesis, modulation of macrophages towards pro-inflammatory phenotype, and reduced number of metastatic lesions in the lungs of mice bearing 4T1 tumors. Our results therefore suggest that IL-31 is a multi-targeted agent that can affect both tumor and host-derived protumorigenic cells. This study will pave the way toward the development of a novel anti-cancer modality affecting primary tumors and their metastasis.