The price of immune awakening: bridging knowledge gaps in checkpoint inhibitor-related pneumonitis in lung cancer

Immune checkpoint inhibitors have transformed lung cancer therapy, offering durable tumour control and improved survival. Yet their success has revealed a paradox: checkpoint inhibitor-related pneumonitis (CIP), an unpredictable immune-mediated complication that can damage the lungs. CIP differs from cytotoxic therapy-induced pneumonitis, arising from immune dysregulation rather than direct tissue injury, and presents with diverse clinical and radiological patterns. Incidence ranges from 2.5% in trials to nearly 20% in real-world practice, reflecting biological variability and inconsistent recognition. This viewpoint reviews persistent gaps in understanding CIP, including mechanisms, risk prediction, early detection, and management. CIP appears multifactorial, involving T-cell-driven inflammation, age-related immune changes, and possible environmental or infectious triggers. Risk stratification remains limited, although emerging biomarkers and tumour-or therapy-related factors show potential. Diagnosis relies primarily on exclusion, supported by imaging and bronchoalveolar lavage. Investigational tools, including radiomics and artificial intelligence, demonstrate potential to detect subclinical changes and classify CIP patterns, offering promise for earlier and more objective recognition in the future. Addressing these gaps requires prospective, multidisciplinary research, standardised frameworks, and collaborative registries. CIP represents both a clinical challenge and a scientific opportunity: understanding its mechanisms and improving early recognition may optimise immunotherapy safety, efficacy, and ultimately patient survival and quality of life.