1. Immune checkpoint inhibitor treatment induces colitis with heavy infiltration of CD8+T cells and an infiltration pattern that resembles ulcerative colitis
- Author
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Gerard Dijkstra, Marijn C. Visschedijk, Remco J. Renken, Henk J. Buikema, Marco R. de Groot, Jacco J de Haan, Mathilde Jalving, Gursah Kats-Ugurlu, Sara Hone Lopez, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Perceptual and Cognitive Neuroscience (PCN), Groningen Institute for Organ Transplantation (GIOT), Translational Immunology Groningen (TRIGR), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), and Targeted Gynaecologic Oncology (TARGON)
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Adolescent ,Colon ,medicine.medical_treatment ,Biopsy ,Graft vs Host Disease ,MELANOMA ,Immune checkpoint inhibitor ,Inflammatory bowel disease ,Pathology and Forensic Medicine ,Young Adult ,Immune system ,Crohn Disease ,VERSUS-HOST-DISEASE ,medicine ,Cytotoxic T cell ,Humans ,Colitis ,IMMUNOTHERAPY ,Molecular Biology ,Immune Checkpoint Inhibitors ,Aged ,RISK ,Acute graft-versus-host disease ,business.industry ,Macrophages ,Cell Biology ,General Medicine ,Immunotherapy ,ASSOCIATION ,Middle Aged ,medicine.disease ,Ulcerative colitis ,Immunohistochemistry ,digestive system diseases ,Phenotype ,CD8-positive T-lymphocytes ,Colitis, Ulcerative ,Female ,Original Article ,business ,Infiltration (medical) ,CD8 - Abstract
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
- Published
- 2021