Immune checkpoint inhibitor treatment induces colitis with heavy infiltration of CD8 + T cells and an infiltration pattern that resembles ulcerative colitis

• Published in: Virchows Archiv : an international journal of pathology 2021-12, Vol.479 (6), p.1119-1129
• Main Authors: Hone Lopez, Sara, Kats-Ugurlu, Gursah, Renken, Remco J., Buikema, Henk J., de Groot, Marco R., Visschedijk, Marijn C., Dijkstra, Gerard, Jalving, Mathilde, de Haan, Jacco J.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Biopsy; CD4 antigen; CD8 antigen; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; Colitis - chemically induced; Colitis - immunology; Colitis - pathology; Colitis, Ulcerative - immunology; Colitis, Ulcerative - pathology; Colon; Colon - drug effects; Colon - immunology; Colon - pathology; Comparative analysis; Crohn Disease - immunology; Crohn Disease - pathology; Crohn's disease; Cytotoxicity; Female; Graft versus host disease; Graft vs Host Disease - immunology; Graft vs Host Disease - pathology; Graft-versus-host reaction; Grafting; Helper cells; Humans; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - adverse effects; Immune system; Immunohistochemistry; Infiltration; Inflammatory bowel disease; Inhibitors; Lymphocytes; Lymphocytes T; Macrophages; Macrophages - drug effects; Macrophages - immunology; Male; Medicine; Medicine & Public Health; Middle Aged; Mucosa; Original; Original Article; Pathology; Phenotype; Ulcerative colitis; Young Adult
• ISSN: 0945-6317; 1432-2307
• DOI: 10.1007/s00428-021-03170-x

Colitis is a common, but poorly understood, adverse event of immune checkpoint inhibitors that are standard-of-care for an expanding range of cancer types. This explorative study aimed to describe the immune infiltrates in the colon from individuals developing checkpoint inhibitor colitis and compare them to well-known immunophenotypes of acute graft-versus-host disease, ulcerative colitis, and Crohn’s disease. Colon biopsies ( n  = 20 per group) of patients with checkpoint inhibitor colitis, acute graft-versus-host disease, ulcerative colitis and Crohn’s disease, all colitis treatment-naïve, and of individuals with a normal colon were analyzed using immunohistochemistry: CD8 for cytotoxic T cells, CD4 for T helper cells, and CD68 to identify cells of macrophage lineage. CD8 + T cell, CD4 + T cell, and CD68 + cell counts were performed. Cell infiltration was scored as scattered/patchy or band-like in the superficial and deep gut mucosa. Checkpoint inhibitor colitis was found to be heavily infiltrated by CD8 + T cells. Comparative analysis between groups showed that both CD8 + T cell counts ( P