Multiplexed imaging reveals an IFN-γ-driven inflammatory state in nivolumab-associated gastritis
Year: 2021
Type: article
Study design: Case Report
Abstract: Immune checkpoint blockade using PD-1 inhibition is an effective approach for treating a wide variety of cancer subtypes. While lower gastrointestinal (GI) side effects are more common, upper gastrointestinal adverse events are rarely reported. Here, we present a case of nivolumab-associated autoimmune gastritis. To elucidate the immunology underlying this condition, we leverage multiplexed ion beam imaging by time-of-flight (MIBI-TOF) to identify the presence and proportion of infiltrating immune cells from a single section of biopsy specimen. Using MIBI-TOF, we analyze formalin-fixed, paraffin-embedded human gastric tissue with 28 labels simultaneously. Our analyses reveal a gastritis characterized by severe mucosal injury, interferon gamma (IFN-γ)-producing gastric epithelial cells, and mixed inflammation that includes CD8 and CD4 T cell infiltrates with reduced expression of granzyme B and FOXP3, respectively. Here, we provide a comprehensive multiplexed histopathological mapping of gastric tissue, which identifies IFN-γ-producing epithelial cells as possible contributors to the nivolumab-associated gastritis.
Source: Cell Reports Medicine
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,200
Funders: National Science Foundation, U.S. Department of Defense, Bill and Melinda Gates Foundation, Damon Runyon Cancer Research Foundation, National Institutes of Health, National Institute on Aging, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, Division of Electrical, Communications and Cyber Systems, Hyundai Hope On Wheels, Stanford Cancer Institute
Awards: G1294626703, G1333989588, G1679878676, G2328161403, G2348990056, G2521557779, The Phenotypic Landscape of Cognitive Decline as Revealed by Next-Generation Multiplexed Ion Beam Imaging, G3531549433, Predictive signatures in breast cancer using multiplexed ion beam imaging, NNCI: Stanford University - SNSF, SNF, MAF, EMF, G3906154788, MIRIAD - Multiplexed Imaging of Resilience In Alzheimers Disease, G4484938617, G4819111990, G4919389345, G5090992868, G5116334056, G5398508105, G5416592815, G562087445, G6808397418, G7020380496, G7115553444, G726778916, G7449511227, Molecular and Cellular Immunobiology, G7708392061, Stanford Cooperative Research Center for Novel, Alternative Model Systems for Enteric Diseases, G8715556579, G9000036163, G9000173002, G9000185564, G9000293380, G9000302151, Integrated Genomic and Functional Studies of Immunotherapy for Multi-Food Allergy, Stanford Cancer Immune Monitoring and Analysis Center (CIMAC)
OpenAlex ID: W3205860754