Immune checkpoint inhibitor-related pneumonitis: From guidelines to the front lines

Immune checkpoint inhibitors (ICIs) have changed cancer treatment, evoking durable responses in various cancers. However, their immune-mediated mechanisms can lead to unique toxicities known as immune-related adverse events (irAEs), among which ICI-related pneumonitis (ICI-P) is a critical concern owing to its potential severity and impact on treatment continuity. This review provides a comprehensive overview of ICI-P, covering its epidemiology, pathophysiology, clinical features, diagnosis, risk factors, and treatments. ICI-P is more frequently observed in real-world settings than in clinical trials, especially in patients with risk factors such as pre-existing interstitial lung disease. The pathogenesis of ICI-P involves Th1/Th17 inflammation and autoantibody production, but the exact mechanisms remain unclear. An organizing pneumonia-like pattern is a characteristic radiological finding on chest computed tomography. Diagnosis can be supported by the evaluation of biomarkers like Krebs von den Lungen-6 and surfactant protein-D. High-dose corticosteroids are the standard treatment, although optimal regimens remain under investigation. Relapse is not uncommon, particularly in cases with an organizing pneumonia-like pattern or prolonged exposure to ICIs. Resuming ICIs after ICI-P is associated with a marked risk of relapse and must be carefully considered. Notably, immune modulation by ICIs may persist after discontinuation, potentially increasing susceptibility to drug-induced pneumonitis from subsequent therapies. As the use of ICIs expands, enhanced recognition, timely intervention, and individualized management of ICI-P are essential. Future strategies incorporating biomarkers, real-world data, and artificial intelligence may further improve outcomes for patients with ICI-P.