Delineating the pathogenesis of immune checkpoint-inhibitor (ICI)-associated colitis
T cell checkpoint inhibitor (TCI)-associated colitis affects 22% of patients treated with anti-CTLA-4/PD-1 therapy and 6% treated with anti-PD-1 therapy. Management includes corticosteroids and anti-TNFα therapy, although treatment refractory cases occur. We characterized gut-isolated lymphocytes from patients with TCI-associated colitis by flow cytometry and NanoString analysis, aiming to delineate disease pathogenesis. Colon biopsies were obtained from patients with anti-PD-1-associated colitis, anti-PD-1 treated with no colitis, anti-CTLA-4/PD1 “dual-checkpoint inhibitor” colitis, anti-CTLA-4/PD-1 treated with no colitis, ulcerative colitis, and healthy volunteers. Lymphocytes were extracted and stained for markers of T cells, activation, mucosal-associated invariant T (MAIT) cells, regulatory T cells (Treg) and cytotoxicity prior to flow-cytometry. RNA samples were analyzed using the nCounter® Autoimmune Profiling Panel on the nCounter® Sprint.
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