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  • Title: Multiplexed imaging reveals an IFN-γ-driven inflammatory state in nivolumab-associated gastritis.
    Author: Ferrian S, Liu CC, McCaffrey EF, Kumar R, Nowicki TS, Dawson DW, Baranski A, Glaspy JA, Ribas A, Bendall SC, Angelo M.
    Journal: Cell Rep Med; 2021 Oct 19; 2(10):100419. PubMed ID: 34755133.
    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.
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