CD8⁺ Lymphocyte Infiltration Is a Specific Feature of Colitis Induced by Immune Checkpoint Inhibitors

Immune checkpoint inhibitors (ICPIs) have revolutionized cancer therapy, although immune-related adverse events (irAEs) remain a serious issue. The clinical characteristics of colitis induced by ICPIs are very similar to inflammatory bowel disease. Recently, cluster of differentiation 8 positive (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.

Newly diagnosed and untreated patients were retrospectively enrolled. Biopsy specimens were obtained from endoscopic areas of high inflammation for immunohistochemical analysis of the number of cluster of differentiation 4 positive (CD4⁺) and CD8⁺ lymphocytes in the high-powered microscopic field with the most inflammation.

A total of 102 patients [12 with irAE colitis, 37 with ulcerative colitis (UC), 22 with Crohn's disease (CD), and 31 with ischemic colitis (IC)] were analyzed. 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 versus UC, CD, and IC, respectively). The optimal cutoff CD8⁺/CD4⁺ ratio for diagnosing irAE colitis was 1.17 (sensitivity 83%, specificity 84%). The optimal cutoff number of CD8⁺ lymphocytes for diagnosing irAE colitis was 102 cells per high-power field (sensitivity 75%, specificity 81%).

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.