The JAK-STAT Pathway as a Therapeutic Strategy in Cancer Patients with Immune Checkpoint Inhibitor-Induced Colitis: A Narrative Review

Simple Summary Clinical management of some cancers requires immunotherapy using immune checkpoint inhibitors (ICI). ICI, however, can result in severe gastrointestinal toxicity, including ICI colitis. The main guidelines recommend the use of corticosteroids or some biologic drugs such as infliximab or vedolizumab. However, little space is given to Janus kinase (JAK)-signal transducer and activator of transcription (STAT) inhibitors. This review summarizes the primary evidence for using JAK-STAT inhibitors in managing ICI colitis. Tofacitinib has been provided in multiple case reports of being able to induce solid clinical remission of ICI colitis without concerns for the oncologic progression of the underlying neoplasm under immunotherapy treatment.Abstract Immunotherapy has emerged as a pivotal component in the treatment of various malignancies, encompassing lung, skin, gastrointestinal, and head and neck cancers. The foundation of this therapeutic approach lies in immune checkpoint inhibitors (ICI). While ICIs have demonstrated remarkable efficacy in impeding the neoplastic progression of these tumours, their use may give rise to substantial toxicity, notably in the gastrointestinal domain, where ICI colitis constitutes a significant aspect. The optimal positioning of Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway inhibitors in the therapeutic management of ICI colitis remains unclear. Numerous reports have highlighted notable improvements in ICI colitis through the application of pan-JAK-STAT inhibitors, with tofacitinib, in particular, reporting evident clinical remission of colitis. The precise mechanism by which JAK-STAT inhibitors may impact the pathogenetic process of ICI colitis remains inadequately understood. However, there is speculation regarding their potential role in modulating memory resident CD8+ T lymphocytes. The elucidation of this mechanism requires further extensive and robust evidence, and ongoing JAK-STAT-based trials are anticipated to contribute valuable insights.