Pulmonary toxicity of immune checkpoint immunotherapy

Abstract

Cancer remains a leading cause of mortality on a global scale. Lung cancer, specifically non–small cell lung cancer (NSCLC), is a prominent contributor to this burden. The management of NSCLC has advanced substantially in recent years, with immunotherapeutic agents, such as immune checkpoint inhibitors (ICIs), leading to improved patient outcomes. Although generally well tolerated, the administration of ICIs can result in unique side effects known as immune-related adverse events (irAEs). The occurrence of irAEs involving the lungs, specifically checkpoint inhibitor pneumonitis (CIP), can have a profound effect on both future therapy options and overall survival. Despite CIP being one of the more common serious irAEs, limited treatment options are currently available, in part due to a lack of understanding of the underlying mechanisms involved in its development. In this Review, we aim to provide an overview of the epidemiology and clinical characteristics of CIP, followed by an examination of the emerging literature on the pathobiology of this condition.

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“…Cancer is a formidable disease that poses a significant threat to human health and has been a persistent challenge in the global public health domain ( Ferlay et al, 2015 ; Fitzmaurice et al, 2015 ; Bray et al, 2021 ; Sung et al, 2021 ). Despite notable advances in the medical field, cancer treatment still confronts various limitations and challenges ( Chang et al, 2021 ; Craig et al, 2021 ; Ghanbar and Suresh, 2024 ). Drug therapy stands out as a widely employed approach in cancer treatment ( Wu et al, 2022 ), where the effectiveness and side effects of drugs are pivotal factors influencing treatment outcomes ( Dinić et al, 2020 ; Steinbrueck et al, 2020 ; Li et al, 2024b ).…”

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“…It is also important to note, that immunotherapy in the form of existing ICIs, is not quite as benign as was initially hoped. Significant levels of immunotherapy-related adverse events (irAEs) have been reported in non-small cell lung cancer (NSCLC) ( 68 , 69 ), melanoma ( 70 ) and HNSCC ( 71 ) especially when multiple ICIs are combined. Particularly problematic is the consistent observation that ICI toxicity and effectiveness are extremely correlated suggesting a substantial hurdle to ICI deployment for HNSCC particularly when combined with other toxic regimens/treatments.…”