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

• DOI: 10.1136/jitc-2021-003585
• Publication Date: 2021-12-08T16:56:42Z
• Authors: Amrit S Gonugunta; Mitchell S von It...; 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
• Keywords: Science & Technology; Lung Neoplasms; Drug-Related Side Effects and Adverse Reactions; Humoural immunology and immunochemistry; Brain Neoplasms; Immunology; Case Report; Middle Aged; Antibodies, Monoclonal, Humanized; cytokines; 3. Good health; 03 medical and health sciences; Antineoplastic Agents, Immunological; 0302 clinical medicine; Oncology; Carcinoma, Squamous Cell; Humans; Female; Life Sciences & Biomedicine

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