Checkpoint Inhibitor-Induced Colitis: From Pathogenesis to Management

The advent of immunotherapy, specifically of immune checkpoint inhibitors (ICIs), for the treatment of solid tumors has deeply transformed therapeutic algorithms in medical oncology. Approximately one-third of patients treated with ICIs may de velop immune-related adverse events, and the gastrointestinal tract is often affected by different grades of mucosal inflammation. Checkpoint inhibitors colitis (CIC) presents with watery or bloody diarrhea and, in the case of severe symptoms, requires ICIs discontinuation. The pathogenesis of CIC is multifactorial and still partially unknown: anti-tumor activity that collaterally effects the colonic tissue and the upregulation of specific systemic inflammatory pathways (i.e., CD8+ cytotoxic and CD4+ T lymphocytes) are mainly involved. Many questions remain regarding treatment timing and options, and biological treatment, especially with anti-TNF alpha, can be offered to these patients with the aim of rapidly resuming oncological therapies. CIC shares similar pathogenesis and aspects with inflammatory bowel disease (IBD) and the use of ICI in IBD patients is under evaluation. This review aims to summarize the pathogenetic mechanism underlying CIC and to discuss the current evidenced-based management options, including the role of biological therapy, emphasizing the relevant clinical impact on CIC and the need for prompt recognition and treatment.

Automated summary

The introduction of immunotherapy, particularly immune checkpoint inhibitors (ICIs), has significantly changed the therapeutic algorithms for solid tumors. ICIs can lead to immune-related adverse events, with the gastrointestinal tract being commonly affected by varying levels of mucosal inflammation. The pathogenesis of checkpoint inhibitors colitis (CIC) is multifactorial and not fully understood, involving both anti-tumor activity and upregulation of specific inflammatory pathways. Treatment options for CIC, including biological therapy such as anti-TNF alpha, need to be further explored and prompt recognition and treatment are crucial.