Presentation description

Cancer immunotherapy is a form of cancer treatment that educates the immune system to recognize and attack cancer cells. However, by activating the immune system, we also observe a broad range of immune-mediated side-effects, including the development of autoimmune diabetes. Particularly, immune checkpoint inhibitors (CPIs) are a type of immunotherapy that have improved survival benefits for patients with a range of cancer types. It is important to note that there are currently no biomarkers to identify which patients may be susceptible to the development of CPI-induced immunotoxicity. For this reason, we assessed clinical information from a cohort of stage IV melanoma patients that received CPI treatment alongside the longitudinal serum samples to assess whether differences in cytokine responses could predict the development of CPI-induced diabetes. We hypothesized that cytokines may act as a biomarker for CPI-induced toxicity due to their role in coordinating inflammatory immune responses. We identified that certain cytokines, such as IL-27, appeared to be upregulated preceding initiation of treatment in patients who went on to develop CPI-diabetes. We next wanted to assess the role of IL-27, which is a pleiotropic cytokine that interacts with multiple cell types, in CPI-induced diabetes. Given the upregulation of IL-27 in cancer patients that develop CPI-induced diabetes we next assessed whether mice deficient in IL-27 and are protected against CPI-induced diabetes. Notably, we reduce the development of CPI-induced diabetes in the IL-27-deficient setting, but we also see a reduction in anti-tumor immunity. Next, we are interested in identifying which cells express IL-27 at both homeostasis and in response to CPI treatment in different organs, such as the pancreas and tumor. Together, this study has allowed us to evaluate a potential predictive cytokine profile that may assist in determining how IL-27 could play a role as a biomarker for CPI-induced diabetes susceptibility and to assess its utility as a treatment option to protect against CPI-induced irAEs.