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

Selena Ferrian; Candace C. Liu; Erin F. McCaffrey; Rashmi Kumar; Theodore S. Nowicki; David W. Dawson; Alex Baranski; John A. Glaspy; Antoni Ribas; Sean C. Bendall; Michael Angelo

Cell Reports Medicine (Oct 2021)

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

Selena Ferrian,
Candace C. Liu,
Erin F. McCaffrey,
Rashmi Kumar,
Theodore S. Nowicki,
David W. Dawson,
Alex Baranski,
John A. Glaspy,
Antoni Ribas,
Sean C. Bendall,
Michael Angelo

Affiliations

Selena Ferrian: Department of Pathology, Stanford University, Stanford, CA 94305, USA
Candace C. Liu: Department of Pathology, Stanford University, Stanford, CA 94305, USA
Erin F. McCaffrey: Department of Pathology, Stanford University, Stanford, CA 94305, USA
Rashmi Kumar: Department of Pathology, Stanford University, Stanford, CA 94305, USA
Theodore S. Nowicki: Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
David W. Dawson: Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA 90095, USA
Alex Baranski: Department of Pathology, Stanford University, Stanford, CA 94305, USA
John A. Glaspy: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA 90095, USA; Division of Hematology-Oncology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90024, USA
Antoni Ribas: Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA; Division of Hematology-Oncology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90024, USA; Division of Surgical-Oncology, Department of Surgery, University of California, Los Angeles, Los Angeles, CA 90024, USA; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Parker Institute for Cancer Immunotherapy, San Francisco, CA 94129, USA
Sean C. Bendall: Department of Pathology, Stanford University, Stanford, CA 94305, USA; Parker Institute for Cancer Immunotherapy, San Francisco, CA 94129, USA
Michael Angelo: Department of Pathology, Stanford University, Stanford, CA 94305, USA; Corresponding author

Journal volume & issue: Vol. 2, no. 10
p. 100419

Abstract

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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.

Published in Cell Reports Medicine

ISSN: 2666-3791 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Medicine (General)
Website: https://www.cell.com/cell-reports-medicine

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