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

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-associate...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2021-10-01
Series:Cell Reports Medicine
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2666379121002810
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author 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
author_facet 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
author_sort Selena Ferrian
collection DOAJ
description 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.
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spelling doaj.art-d8846dbc858c49c3bc533ed8d39457652022-12-21T22:37:49ZengElsevierCell Reports Medicine2666-37912021-10-01210100419Multiplexed imaging reveals an IFN-γ-driven inflammatory state in nivolumab-associated gastritisSelena Ferrian0Candace C. Liu1Erin F. McCaffrey2Rashmi Kumar3Theodore S. Nowicki4David W. Dawson5Alex Baranski6John A. Glaspy7Antoni Ribas8Sean C. Bendall9Michael Angelo10Department of Pathology, Stanford University, Stanford, CA 94305, USADepartment of Pathology, Stanford University, Stanford, CA 94305, USADepartment of Pathology, Stanford University, Stanford, CA 94305, USADepartment of Pathology, Stanford University, Stanford, CA 94305, USADepartment 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, USAJonsson 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, USADepartment of Pathology, Stanford University, Stanford, CA 94305, USADepartment 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, USAEli 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, USADepartment of Pathology, Stanford University, Stanford, CA 94305, USA; Parker Institute for Cancer Immunotherapy, San Francisco, CA 94129, USADepartment of Pathology, Stanford University, Stanford, CA 94305, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2666379121002810programmed death 1nivolumabgastritisMIBI-TOFinterferon gammaIFN-γ
spellingShingle 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
Multiplexed imaging reveals an IFN-γ-driven inflammatory state in nivolumab-associated gastritis
Cell Reports Medicine
programmed death 1
nivolumab
gastritis
MIBI-TOF
interferon gamma
IFN-γ
title Multiplexed imaging reveals an IFN-γ-driven inflammatory state in nivolumab-associated gastritis
title_full Multiplexed imaging reveals an IFN-γ-driven inflammatory state in nivolumab-associated gastritis
title_fullStr Multiplexed imaging reveals an IFN-γ-driven inflammatory state in nivolumab-associated gastritis
title_full_unstemmed Multiplexed imaging reveals an IFN-γ-driven inflammatory state in nivolumab-associated gastritis
title_short Multiplexed imaging reveals an IFN-γ-driven inflammatory state in nivolumab-associated gastritis
title_sort multiplexed imaging reveals an ifn γ driven inflammatory state in nivolumab associated gastritis
topic programmed death 1
nivolumab
gastritis
MIBI-TOF
interferon gamma
IFN-γ
url http://www.sciencedirect.com/science/article/pii/S2666379121002810
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