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 a...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2025-08-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/13/8/e011818.full |
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| author | Todd M Brusko Ana Luisa Perdigoto Kevan C Herold Zoe Quandt Arabella Young Garry Nolan Jee Hye Kang Mark S Anderson Paul L Bollyky Graham Larson Barlow Jennifer A Smith Irina Kusmartseva Shen Dong Melanie R Shapiro Jamie L Felton Vinh Q Nguyen Greg Szot Assad A Hassoun Maki Nakayama Stewart Cooper |
| author_facet | Todd M Brusko Ana Luisa Perdigoto Kevan C Herold Zoe Quandt Arabella Young Garry Nolan Jee Hye Kang Mark S Anderson Paul L Bollyky Graham Larson Barlow Jennifer A Smith Irina Kusmartseva Shen Dong Melanie R Shapiro Jamie L Felton Vinh Q Nguyen Greg Szot Assad A Hassoun Maki Nakayama Stewart Cooper |
| author_sort | Todd M Brusko |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ac7c7def11f54dac95a3a7702d3fe0ac |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-ac7c7def11f54dac95a3a7702d3fe0ac2025-08-20T03:41:34ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262025-08-0113810.1136/jitc-2025-011818Autoimmune origin for immune checkpoint inhibitor-diabetes revealed by deep immune phenotyping of the pancreasTodd M Brusko0Ana Luisa Perdigoto1Kevan C Herold2Zoe Quandt3Arabella Young4Garry Nolan5Jee Hye Kang6Mark S Anderson7Paul L Bollyky8Graham Larson Barlow9Jennifer A Smith10Irina Kusmartseva11Shen Dong12Melanie R Shapiro13Jamie L Felton14Vinh Q Nguyen15Greg Szot16Assad A Hassoun17Maki Nakayama18Stewart Cooper19Department of Pediatrics, University of Florida, Gainesville, Florida, USADepartment of Internal Medicine, Yale University, New Haven, Connecticut, USADepartment of Internal Medicine, Yale University, New Haven, Connecticut, USADepartment of Medicine, University of California San Francisco, San Francisco, California, USADiabetes Center, University of California San Francisco, San Francisco, California, USADepartment of Pathology, Stanford University School of Medicine, Stanford, California, USADiabetes Center, University of California San Francisco, San Francisco, California, USADepartment of Medicine, University of California San Francisco, San Francisco, California, USADivision of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, USADivision of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, USADiabetes Center, University of California San Francisco, San Francisco, California, USADepartment of Pathology, Immunology and Laboratory Medicine, University of Florida Diabetes Institute, Gainesville, Florida, USADiabetes Center, University of California San Francisco, San Francisco, California, USADepartment of Pathology, Immunology and Laboratory Medicine, University of Florida Diabetes Institute, Gainesville, Florida, USADepartment of Pediatrics, Division of Pediatric Endocrinology and the Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, USADepartment of Surgery, University of California San Francisco, San Francisco, California, USADiabetes Center, University of California San Francisco, San Francisco, California, USADepartment of Surgery, California Pacific Medical Center, San Francisco, California, USADepartment of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USALiver Center, University of California San Francisco, San Francisco, California, USAImmune 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.https://jitc.bmj.com/content/13/8/e011818.full |
| spellingShingle | Todd M Brusko Ana Luisa Perdigoto Kevan C Herold Zoe Quandt Arabella Young Garry Nolan Jee Hye Kang Mark S Anderson Paul L Bollyky Graham Larson Barlow Jennifer A Smith Irina Kusmartseva Shen Dong Melanie R Shapiro Jamie L Felton Vinh Q Nguyen Greg Szot Assad A Hassoun Maki Nakayama Stewart Cooper Autoimmune origin for immune checkpoint inhibitor-diabetes revealed by deep immune phenotyping of the pancreas Journal for ImmunoTherapy of Cancer |
| title | Autoimmune origin for immune checkpoint inhibitor-diabetes revealed by deep immune phenotyping of the pancreas |
| title_full | Autoimmune origin for immune checkpoint inhibitor-diabetes revealed by deep immune phenotyping of the pancreas |
| title_fullStr | Autoimmune origin for immune checkpoint inhibitor-diabetes revealed by deep immune phenotyping of the pancreas |
| title_full_unstemmed | Autoimmune origin for immune checkpoint inhibitor-diabetes revealed by deep immune phenotyping of the pancreas |
| title_short | Autoimmune origin for immune checkpoint inhibitor-diabetes revealed by deep immune phenotyping of the pancreas |
| title_sort | autoimmune origin for immune checkpoint inhibitor diabetes revealed by deep immune phenotyping of the pancreas |
| url | https://jitc.bmj.com/content/13/8/e011818.full |
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