Alpha-CTLA-4 mAb-associated panenteritis: a histologic and immunohistochemical analysis

Area of Science:

• Immunology
• Gastroenterology
• Oncology

Background:

• Monoclonal antibodies (mAbs) targeting cytotoxic T lymphocyte antigen-4 (CTLA-4) are used in cancer immunotherapy.
• While effective, these mAbs can cause adverse effects, including severe gastroenteritis.

Purpose of the Study:

• To investigate the gastrointestinal toxicity observed in patients treated with alpha-CTLA-4 mAbs.
• To characterize the endoscopic and histologic findings of this toxicity.

Main Methods:

• Observation of 5 patients with severe gastrointestinal toxicity.
• Endoscopic examination of gastric, small intestinal, and colonic mucosa.
• Histologic analysis and immunohistochemical staining of biopsies.

Main Results:

• Variable endoscopic findings from normal to erythematous and ulcerated mucosa.
• Consistent histologic findings: lymphoplasmacytic expansion, increased intraepithelial lymphocytes, and epithelial apoptosis.
• Increased T-cell subsets (CD3+, CD4+, CD8+) and CD4CD25 regulatory T cells in the gastrointestinal mucosa.

Conclusions:

• Gastrointestinal toxicity associated with alpha-CTLA-4 mAbs resembles autoimmune enteropathy.
• Increased regulatory T cells in the gut mucosa may contribute to the pathogenesis of this immune-related adverse event.