Modulating checkpoint molecules in inflammatory bowel diseases as a new therapeutic strategy: a narrative review

Inflammatory bowel diseases (IBD) are complex, multifactorial disorders characterized by a dysregulated immune response. While recent years have seen the emergence of numerous advanced therapies targeting inflammatory cytokines and their associated signaling pathways, achieving high rates of sustained remission remains a significant challenge. Stimulatory and inhibitory immune checkpoints, which are induced upon T cell activation, play a critical role in fine-tuning the immune response. Immune checkpoint inhibitors, by restoring T cell activity, have revolutionized cancer treatment. Conversely, modulating checkpoint molecules offers a promising strategy to dampen the excessive immune response observed in immune-mediated inflammatory diseases (IMIDs) such as IBD. In this review, we provide a comprehensive overview of immune checkpoint molecules, explore the rationale for targeting them in IBD, and summarize current evidence from clinical trials investigating checkpoint modulation in IMIDs.