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

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Gonugunta, Amrit S
von Itzstein, Mitchell S
Mu-Mosley, Hong
Fattah, Farjana
Farrar, J David
Mobely, Angela
Rashdan, Sawsan
Lai, Sunny
Bhai, Salman F
Bermas, Bonnie L
Karp, David
Li, Quan-Zhen
Wakeland, Edward K
Gerber, David E
Griffith University Author(s)
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2021
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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.

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Journal for ImmunoTherapy of Cancer

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9

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12

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© Author(s) (or their employer(s)) 2021. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/.

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Humoural immunology and immunochemistry

Science & Technology

Life Sciences & Biomedicine

Oncology

Immunology

cytokines

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Gonugunta, AS; von Itzstein, MS; Mu-Mosley, H; Fattah, F; Farrar, JD; Mobely, A; Rashdan, S; Lai, S; Bhai, SF; Bermas, BL; Karp, D; Li, Q-Z; Wakeland, EK; Gerber, DE, Humoral and cellular correlates of a novel immune-related adverse event and its treatment, Journal for ImmunoTherapy of Cancer, 2021, 9 (12), pp. e003585

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