Multiplexed imaging reveals an IFN-γ-driven inflammatory state in nivolumab-associated gastritis

ABSTRACT: Summary 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. Graphical abstract Highlights Multiplexed imaging of gastric toxicity associated with anti-PD-1 immunotherapy Analysis reveals severe mucosal injury associated with IFN-γ-expressing epithelial cells Inflamed gastric epithelium is accompanied by mixed infiltration of CD4 and CD8 T cells Ferrian et al. leverage multiplexed ion beam imaging by time-of-flight to characterize a case of anti-PD-1-associted autoimmune gastritis. This study reveals gastritis characterized by severe mucosal injury, IFN-γ-producing gastric epithelial cells, and inflammation that includes CD8 and CD4 T cell infiltrates with reduced expression of granzyme B and FOXP3, respectively.

SUBMITTER: Ferrian S 

PROVIDER: S-EPMC8561237 | biostudies-literature |

REPOSITORIES: biostudies-literature