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

Autoimmune origin for immune checkpoint inhibitor-diabetes revealed by deep immune phenotyping of the pancreas. Journal for immunotherapy of cancer Quandt, Z., Young, A., Barlow, G. L., Smith, J. A., Kusmartseva, I., Dong, S., Shapiro, M. R., Kang, J. H., Felton, J. L., Nguyen, V. Q., Szot, G., Hassoun, A. A., Perdigoto, A. L., Herold, K. C., Nolan, G., Bollyky, P. L., Brusko, T. M., Nakayama, M., Cooper, S., Anderson, M. S. 2025; 13 (8)

Abstract

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.

View details for DOI 10.1136/jitc-2025-011818

View details for PubMedID 40813111