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CD8+ Lymphocyte Infiltration Is a Specific Feature of Colitis Induced by Immune Checkpoint Inhibitors
Yoshiyuki Takahashi1, Tadanobu Nagaya2, Yugo Iwaya1
1Department of Gastroenterology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan.
Insights
Immune checkpoint inhibitor colitis shows higher CD8+ T-cell infiltration than other colitis types. Increased CD8+/CD4+ T-cell ratios can help distinguish this immune-related adverse event.
Area of Science:
- Oncology
- Immunology
- Gastroenterology
Background:
- Immune checkpoint inhibitors (ICPIs) offer revolutionary cancer therapy but can cause immune-related adverse events (irAEs).
- Colitis induced by ICPIs shares clinical similarities with inflammatory bowel disease (IBD).
- CD8+ lymphocyte infiltration is increasingly linked to irAE development.
Purpose of the Study:
- To compare CD8+ lymphocyte infiltration in ICPI-induced colitis (irAE colitis) with other colitis types.
- To identify potential histological biomarkers for differentiating irAE colitis.
Main Methods:
- Retrospective analysis of biopsy specimens from 102 patients with irAE colitis, ulcerative colitis (UC), Crohn's disease (CD), and ischemic colitis (IC).
- Immunohistochemical analysis to quantify CD4+ and CD8+ lymphocytes in inflamed areas.
- Comparison of CD8+ lymphocyte counts and CD8+/CD4+ ratios across different colitis groups.
Main Results:
- irAE colitis exhibited significantly higher CD8+ lymphocyte infiltration compared to CD4+ lymphocytes (p<0.01).
- CD8+ lymphocyte infiltration and the CD8+/CD4+ ratio were significantly elevated in irAE colitis versus UC, CD, and IC (p<0.05 or p<0.01).
- Optimal cutoffs for diagnosis were a CD8+/CD4+ ratio of 1.17 (83% sensitivity, 84% specificity) and 102 CD8+ cells/HPF (75% sensitivity, 81% specificity).
Conclusions:
- Elevated CD8+ lymphocyte infiltration is a key feature of irAE colitis.
- A higher CD8+/CD4+ T-cell ratio serves as a potential biomarker for distinguishing irAE colitis.
- These histological findings offer simple, useful diagnostic markers for irAE colitis.
Background:
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.
Methods:
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.
Results:
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%).
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.
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