Autoimmune origin for immune checkpoint inhibitor-diabetes revealed by deep immune phenotyping of the pancreas
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.
Authors
- Jamie L. Felton (ORCID: https://orcid.org/0000-0002-6170-1156)
- Maki Nakayama (ORCID: https://orcid.org/0000-0002-0009-3687)
- Zoe Quandt (ORCID: https://orcid.org/0000-0002-4568-4368)
- Ana Luisa Perdigoto (ORCID: https://orcid.org/0000-0002-0348-9329)
- Kevan C. Herold (ORCID: https://orcid.org/0000-0003-1534-6613)
- Garry P. Nolan (ORCID: https://orcid.org/0000-0002-8862-9043)
- Irina Kusmartseva (ORCID: https://orcid.org/0000-0003-2614-0813)
- Shen Dong (ORCID: https://orcid.org/0000-0001-8839-7046)
- Arabella Young (ORCID: https://orcid.org/0000-0002-6845-9753)
- Graham L. Barlow (ORCID: https://orcid.org/0000-0001-9335-5414)
- Paul L. Bollyky (ORCID: https://orcid.org/0000-0003-2499-9448)
- Melanie R. Shapiro (ORCID: https://orcid.org/0000-0003-2090-0877)
- Stewart Cooper (ORCID: https://orcid.org/0000-0002-5307-8982)
- Todd M. Brusko (ORCID: https://orcid.org/0000-0003-2878-9296)
- Jee Hye Kang
- Vinh Nguyen (ORCID: https://orcid.org/0000-0001-9564-9037)
- Gregory L. Szot (ORCID: https://orcid.org/0000-0002-3921-049X)
- Mark Stuart Anderson (ORCID: https://orcid.org/0000-0002-3093-4758)
- Jennifer Smith (ORCID: https://orcid.org/0000-0002-5662-1776)
- Assad Hassoun
Institutions
- University of California, San Francisco (US)
- University of Utah (US)
- San Francisco Zoo (US)
- Huntsman Cancer Institute (US)
- California Pacific Medical Center (US)
- Yale University (US)
- University of Florida (US)
- VA Connecticut Healthcare System (US)
- Indiana University School of Medicine
- Indiana University – Purdue University Indianapolis (US)
- University of San Francisco (US)
- Tishk International University (IQ)
- University of Colorado Denver (US)
- Stanford University (US)
Publication Details
- Journal
- Journal for ImmunoTherapy of Cancer
- Published
- 2025-08-01
- DOI
- https://doi.org/10.1136/jitc-2025-011818
- Citations
- 2
- Primary Topic
- Diabetes and associated disorders
- Type
- article
- Field-Weighted Citation Impact
- 3.63