Humoral and cellular correlates of a novel immune-related adverse event and its treatment

Amrit S. Gonugunta, Mitchell S. Von Itzstein, Hong Mu-Mosley, Farjana Fattah, J. David Farrar, Angela Mobely, Sawsan Rashdan, Sunny Lai, Salman F. Bhai, Bonnie L. Bermas, David Karp, Quan-zhen Li, Edward K. Wakeland, David E. Gerber

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Immune-related adverse events (irAE) may affect almost any organ system and occur at any point during treatment with immune checkpoint inhibitors (ICI). We present a patient with advanced lung cancer receiving antiprogrammed death 1 checkpoint inhibitor who developed a delayed-onset visual irAE treated with corticosteroids. Through assessment of longitudinal biospecimens, we analyzed serial autoantibodies, cytokines, and cellular populations. Months after ICI initiation and preceding clinical toxicity, the patient developed broad increases in cytokines (most notably interleukin-6 (IL-6), interferon-γ(IFN 3), C-X-C motif chemokine ligand 2 (CXCL2), and C-C motif chemokine ligand 17 (CCL17)), autoantibodies (including anti-angiotensin receptor, α-actin, and amyloid), CD8 T cells, and plasmablasts. Such changes were not observed in healthy controls and ICI-treated patients without irAE. Administration of corticosteroids resulted in immediate and profound decreases in cytokines, autoantibodies, and inflammatory cells. This case highlights the potential for late-onset changes in humoral and cellular immunity in patients receiving ICI. It also demonstrates the biologic effects of corticosteroids on these parameters. Application of humoral and cellular immune biomarkers across ICI populations may inform toxicity monitoring and management.

Original languageEnglish (US)
Article numbere003585
JournalJournal for ImmunoTherapy of Cancer
Volume9
Issue number12
DOIs
StatePublished - Dec 8 2021

Keywords

  • antibodies
  • autoimmunity
  • biomarkers
  • cytokines
  • immunotherapy
  • neoplasm
  • tumor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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