PD-1 inhibitor gastroenterocolitis: case series and appraisal of 'immunomodulatory gastroenterocolitis'

Area of Science:

• Gastroenterology
• Oncology
• Immunology

Background:

• Programmed cell death protein 1 (PD-1) inhibitors are crucial in cancer therapy, improving survival for melanoma patients.
• These immunotherapies can induce autoimmune-like side effects, notably gastrointestinal (GI) inflammation.
• Histopathological characteristics of PD-1 inhibitor-induced GI pathology remain under-investigated.

Purpose of the Study:

• To investigate the clinicopathological and histopathological features of gastrointestinal inflammation caused by PD-1/PD-L1 inhibitors.
• To identify key histological findings that differentiate PD-1 inhibitor-induced enterocolitis from other GI conditions.

Main Methods:

• Retrospective analysis of 37 GI tract biopsies from 20 patients treated with PD-1 or PD-L1 inhibitors.
• Evaluation of clinical symptoms, endoscopic findings, and histopathological features.

Main Results:

• Diarrhea was the most frequent symptom; endoscopic findings varied from erythema to ulceration.
• Common histological features included lamina propria expansion, villous blunting, intra-epithelial neutrophils, and increased crypt apoptosis.
• Intra-epithelial lymphocytes were not typically prominent, and crypt rupture with granulomatous response was observed in some cases.

Conclusions:

• PD-1/PD-L1 inhibitors can induce gastritis, enteritis, and colitis with distinct histological patterns.
• Distinguishing PD-1 inhibitor gastroenterocolitis from mimics like IBD or CMV infection relies on clinical history, absence of prominent intra-epithelial lymphocytes, and specific features like crypt rupture.