University of California, San Francisco

Mechanisms of Autoimmune Diabetes Provoked by Cancer Immunotherapy

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Within the last decade, immune checkpoint inhibitors (CPIs) have changed the landscape of cancer care, but also heightened risk for a range of novel side effects called immune related adverse events (irAEs). One important but rare irAE is insulin dependent autoimmune diabetes (CPI-DM). Within this project, Dr Quandt has a multi-pronged approach to address the mechanistic understanding of CPI-DM as a lens to better understand autoimmune diabetes. She will do this by addressing genetic predisposition to CPI-DM by comparing it to genetic risk for type 1 diabetes (T1DM). Next, she will use single cell methodologies to identify patterns of cellular features, transcriptional signatures and T-cell receptors, including cell types and aspects such as cellular activation or exhaustion relative to patients with T1DM and CPI treated patients without CPI-DM with final verification in pancreatic tissue. These studies will contribute to mechanistic understanding of autoimmune diabetes with hope that they may lead to identification of actionable targets that could be used in the prevention or treatment of both CPI-DM and T1DM.