Autoimmune origin for immune checkpoint inhibitor-diabetes revealed by deep immune phenotyping of the pancreas

作者：Zoe Quandt, Arabella Young, Graham L. Barlow, Jennifer Smith, Irina Kusmartseva, Shen Dong, Melanie R. Shapiro, Jee Hye Kang, Jamie L. Felton, Vinh Nguyen, Gregory L. Szot, Assad Hassoun, Ana Luisa Perdigoto, Kevan C. Herold, Garry P. Nolan, Paul L. Bollyky, Todd M. Brusko, Maki Nakayama, Stewart Cooper, Mark S. Anderson · 发表于：Journal for ImmunoTherapy of Cancer · 年份：2025 · DOI：10.1136/jitc-2025-011818 · 被引用次数：3 · 研究领域：Diabetes and associated disorders、Cancer Immunotherapy and Biomarkers、Pancreatic and Hepatic Oncology Research

Immune checkpoint inhibitor-diabetes (CPI-D) is an acute and non-resolving immune-related adverse event (irAE) initiated primarily by disrupting the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) axis with monoclonal antibodies. A major limitation in understanding CPI-D is the lack of access to pancreatic tissue from patients experiencing this complication. We report a unique patient with no prior history of diabetes or autoimmune disease whose treatment with CPI for metastatic melanoma was complicated by CPI-D requiring insulin therapy. The patient then went on to develop pancreatic cancer. In the setting of the pancreatic cancer treatment, we were able to perform detailed single-cell RNA sequencing and immunophenotyping within the surgically resected pancreas. This revealed substantial lymphocytic infiltration associated with the islets, suggestive of an autoimmune rather than autoinflammatory mechanistic origin for CPI-D.