Presentation description

Immune checkpoint inhibitors (CPIs), that target cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD-1), have been proven to increase survival benefits for cancer patients. However, disrupting immunoregulatory molecules can lead to toxicities, known as immune-related adverse events (irAEs). Many irAEs are difficult to understand mechanistically due to difficulty in accessing tissue. Recently, we had the opportunity to look at the pancreas of a cancer patient who had previously developed CPI-induced autoimmune diabetes. By immunohistochemistry, immune cells, particularly B and T lymphocytes were identified to be surrounding the remaining islets. We, therefore, hypothesized that B cells played a role in CPI-induced autoimmune diabetes. Through the use of different autoimmune-prone mouse strains, we can compare the impact on both immune homeostasis in response to CPI treatment. By comparing immune cell data, it was clear that IgH-deficient mice were lacking both B and T cell populations than wild-type NOD mice. We will next assess whether B cell-deficient mice show differences in therapeutic response to CPI treatment relating to both tumor growth and development of autoimmune diabetes and other irAEs. This will provide further insight into how the immune system interacts with CPI treatment and if CPI-induced diabetes can be prevented through different treatment interventions and targeted delivery methods. As a whole, this study has allowed insight into mechanisms by which immune cells interact with cancer cells and self-tissue, which may assist in providing a better understanding of CPI-induced diabetes development and strategies for patients with cancer to mitigate irAEs.