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Checkpoint Inhibitor Colitis Shows Drug-Specific Differences in Immune Cell Reaction That Overlap With Inflammatory

Ying-Chun Lo1, Christina Price2, Kim Blenman3

  • 1Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.

American Journal of Clinical Pathology
|February 8, 2021
PubMed
Abstract

Insights

Checkpoint inhibitor (CPI) colitis shares immune features with inflammatory bowel disease (IBD). Specific immune cell markers like CD8/FoxP3 ratios may predict treatment response in CPI colitis.

Area of Science:

  • Immunology
  • Gastroenterology
  • Oncology

Background:

  • Checkpoint inhibitor (CPI)-associated colitis presents challenges in cancer therapy and resembles inflammatory bowel disease (IBD).
  • Limited research exists on the mechanistic links between CPI colitis and IBD, hindering the identification of shared therapeutic targets.
  • Understanding these similarities could reveal novel treatment strategies for both conditions.

Purpose of the Study:

  • To compare the histological and immunological features of colonic biopsies from patients with CPI colitis and IBD.
  • To identify predictors of infliximab treatment necessity in patients with CPI colitis.

Main Methods:

  • Morphological and inflammatory content of colonic biopsies from anti-CTLA-4 and anti-PD-1/PD-L1 treated patients were analyzed.
  • Biopsy specimens were compared with those from IBD patients.
  • Immune cell markers (CD8, CD4, PD-1, PD-L1, FoxP3, CD68) and their ratios were quantified.

Main Results:

  • CPI colitis biopsies showed lower chronicity but similar activity scores compared to IBD.
  • Anti-CTLA-4 colitis exhibited distinct immune profiles (higher CD8, PD-1, PD-L1, CD68; lower FoxP3) compared to IBD and anti-PD-1/PD-L1 colitis.
  • Higher CD8/FoxP3 ratios and CD68 scores were observed in CPI colitis patients requiring infliximab versus those responding to steroids.

Conclusions:

  • The proinflammatory immune phenotype in anti-CTLA-4 colitis significantly overlaps with IBD.
  • CD8/FoxP3 ratios show potential as predictive biomarkers for therapeutic response in CPI-associated colitis.
Keywords:
Checkpoint inhibitorsColitisImmunohistochemistryInflammatory bowel diseaseT cells

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