The IL-17 family of pro-inflammatory cytokines is involved in the progression of several human diseases. Within the IL-17 family, our group focuses on the role of the IL-17B cytokine and its receptor and cancer and inflammatory diseases.
IL-17B and its receptor, IL-17RB, are upregulated in cancer and correlate to poor prognosis. In vivo, the neutralization of the IL-17B cytokine dramatically impacts tumor progression and survival in several immunocompetent mouse models by a dual mechanism of action on both tumor cells and the tumor microenvironment. First, disruption of IL-17B affects the cancer stem cells, leading to decreased tumorigenic capacity, reduced ability to seed distant tumors and improved response to therapies such as chemotherapy or EGFR inhibitors. Second, the presence of IL-17B also affects the innate immune response: IL-17B-rich tumors exhibit accumulation of exhausted NK cells, and IL-17B may also recruit myeloid cells.
Our group also focuses on the role of the IL-17B-IL-17RB signaling pathway in inflammatory diseases. Among the family of IL-17 cytokines, IL-17A is a major cytokine in psoriasis and anti-IL-17A antibodies exhibit unprecedented clinical activity in moderate to severe psoriasis. We discovered that the IL-17B cytokine is also present in inflammatory settings such arthritis mouse model. Compared to IL-17A, IL-17B is produced by different subsets of inflammatory cells and mediates different proinflammatory responses. Like anti-IL-17A antibodies, targeting IL-17B decreases disease incidence and severity in inflammation mouse models, suggesting that IL-17B is an IL-17A-like but independent target in inflammatory diseases.
Our team has generated various antibodies targeting IL-17B (as well as IL-17A neutralizing antibodies).