Enterocolitis due to immune checkpoint inhibitors: a systematic review

Area of Science:

• Oncology
• Immunology
• Gastroenterology

Background:

• Immune checkpoint inhibitors (ICIs) targeting CTLA-4 and PD-1/PD-L1 are vital cancer therapies.
• Gastrointestinal immune-related adverse effects (irAE) are common and severe complications of ICIs.
• Understanding GI irAE is crucial for optimizing ICI treatment.

Purpose of the Study:

• To systematically review the clinical features, management strategies, and underlying pathophysiology of GI irAE.
• To compare GI irAE associated with anti-CTLA-4 versus anti-PD-1 therapies.
• To explore the role of gut microbiota in ICI response and GI irAE development.

Main Methods:

• Systematic literature review of studies on GI irAE induced by ICIs.
• Analysis of clinical manifestations, management protocols, and pathophysiological mechanisms.
• Investigation of the association between gut microbiota and ICI efficacy/toxicity.

Main Results:

• Anti-CTLA-4 therapy frequently causes severe GI irAE resembling inflammatory bowel disease (IBD).
• Anti-PD-1 therapy-induced GI irAE are less frequent and present with more diverse clinical features.
• Baseline gut microbiota composition correlates with enhanced anti-tumour response and increased susceptibility to ICI-induced enterocolitis.

Conclusions:

• GI irAE management requires tailored approaches based on the specific ICI used.
• Gut microbiota modulation presents a promising avenue for enhancing ICI efficacy and mitigating GI toxicity.
• Further research into gut microbiota manipulation could personalize cancer immunotherapy.