CD8+ Lymphocyte Infiltration is a Specific Feature of Colitis Induced By Immune Checkpoint Inhibitors

Abstract Background Immune checkpoint inhibitors (ICPIs) have revolutionized cancer therapy, although immune-related adverse events (irAEs) remain a severe issue. The clinical characteristics of colitis induced by ICPIs are very similar to inflammatory bowel disease. Recently, CD8+ lymphocyte infiltration into organs has been associated with the onset of irAEs. The present study compared the histological infiltration of CD8+ lymphocytes in irAE colitis with that in other colitis. Methods Among 102 newly diagnosed and untreated patients, 12 with irAE colitis, 37 with ulcerative colitis (UC), 22 with Crohn's disease (CD), and 31 with ischemic colitis (IC) were retrospectively enrolled. Biopsy specimens were obtained from endoscopic areas of high inflammation for immunohistochemical analysis of the number of CD4+ and CD8+ lymphocytes in the most inflamed high-powered microscopic field. Results In irAE colitis, CD8+ lymphocyte infiltration was significantly greater than that of CD4+ lymphocytes (p < 0.01). The amount of CD8+ lymphocyte infiltration was significantly higher in irAE colitis than in UC (p < 0.05), CD (p < 0.05), and IC (p < 0.01). The CD8+/CD4+ ratio was also significantly higher in irAE colitis (p < 0.01 vs. UC, CD, and IC, respectively). The optimal cut-off CD8+/CD4+ ratio for diagnosing irAE colitis was 1.17 (sensitivity: 83%, specificity: 84%). The optimal cut-off the number of CD8+ lymphocytes for diagnosing irAE colitis was 102 cells/high-power field (sensitivity: 75%, specificity: 81%). Conclusions Greater CD8+ lymphocyte infiltration and a higher CD8+/CD4+ ratio may be simple and useful biomarkers to distinguish irAE colitis from other forms of colitis.