Abstract
Immune checkpoint inhibitors (ICIs) have become the standard of care for several cancers. However, ICI therapy has also been associated with various immune-related adverse events (irAEs). Clinical manifestations of immune-related colitis resemble those of inflammatory bowel diseases such as ulcerative colitis (UC). The composition of the bowel microflora is thought to influence the development of inflammatory bowel disease and irAE colitis. We profiled the gene expressions and microbe compositions of colonic mucosa from patients with solid cancers receiving anti-PD-L1 antibody treatment; we then compared the expression profiles associated with irAE colitis with those associated with UC. The pathway enrichment analysis revealed functional similarities between inflamed regions of irAE colitis and UC. The common enriched pathways included leukocyte extravasation and immune responses, whereas non-inflamed mucosa from patients with irAE colitis was distinct from patients with UC and was characterized by the recruitment of immune cells. A similarity between the microbiota profiles was also identified. A decreased abundance of Bacteroides species was observed in inflamed regions from both irAE colitis and UC based on a microbiota composition analysis of 16S rDNA sequencing. Pathways associated with molecule transport systems, including fatty acids, were enriched in inflamed and non-inflamed irAE colitis and inflamed UC, similar to Piphillin-inferred KEGG pathways. While UC is characterized by local regions of inflammation, ICI treatment extends to non-inflammatory regions of the colonial mucosa where immune cells are reconstituted. This analysis of the similarity and heterogeneity of irAE colitis and UC provides important information for the management of irAE colitis.
Highlights
Monoclonal antibodies targeting immune checkpoint cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed death receptor-1 (PD-1) and programmed death ligand 1 (PD-L1), referred to as immune checkpoint inhibitors (ICIs), have become a new standard of care for several cancers including lung cancer and melanoma [1,2,3] as well as renal cell carcinoma [4]
Patients with moderate or severe colitis were frequently observed in ulcerative colitis group compared with immune-related adverse events (irAEs) colitis group, it was not significant
There was no significant difference in grade score between irAE colitis and ulcerative colitis (UC), there was a trend toward higher grade in UC
Summary
Monoclonal antibodies targeting immune checkpoint cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed death receptor-1 (PD-1) and programmed death ligand 1 (PD-L1), referred to as immune checkpoint inhibitors (ICIs), have become a new standard of care for several cancers including lung cancer and melanoma [1,2,3] as well as renal cell carcinoma [4]. Long-term survival is expected in some patients, ICIs could lead to a new class of immune-related adverse events (irAEs), of which gastrointestinal (GI) irAEs are among the most frequent and severe [5, 6]. In their clinical presentation and endoscopic findings, irAE colitis resemble ulcerative colitis (UC) [7, 8]. We have reported on the association between responsiveness to ICI and the gut microbiota [9]. The functional relationship between ICI-induced irAE and the gut microbiota remains unclear
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
