Interactions between interstitial lung abnormalities and immune checkpoint inhibitor therapy in non-small cell lung cancer: A review of current understanding and future directions

Abstract

Immunotherapy has revolutionized the treatment landscape of non-small cell lung cancer (NSCLC), significantly improving survival outcomes and offering renewed hope to patients. However, the presence of interstitial lung abnormalities (ILAs) in patients with NSCLC presents unique challenges, especially due to the elevated risk of immune checkpoint inhibitor (ICI)-related pneumonitis, which can result in treatment interruptions and adversely affect prognosis. ILAs, often detected incidentally on computed tomography imaging, are associated with an increased risk of progression to interstitial lung disease and have been identified as a potential predictor of poor clinical outcomes in patients with NSCLC receiving immunotherapy. This review offers an overview of the current understanding of the interaction between ILAs and ICI therapy, discussing prevalence, radiological features, risk stratification, and management strategies. Additionally, it highlights the need for prospective, multicenter studies to establish optimal treatment modalities for patients with NSCLC having ILAs, to ensure safer and more effective immunotherapy.

Keywords: Non-small cell lung cancer; immune checkpoint inhibitors; immunotherapy; interstitial lung abnormalities; pneumonitis; prognosis.

Figure 1.

Axial CT scans showing subtypes of interstitial lung abnormalities based on the presence or absence of fibrosis. (a) Non-subpleural fibrotic interstitial lung abnormalities (non-SF-ILAs). (b) Subpleural fibrotic interstitial lung abnormalities (SF-ILAs).

Figure 2.

Axial CT scans showing the disappearance of ground-glass opacities due to gravity-dependent atelectasis and insufficient inspiration. (a) A chest CT scan performed with the patient in the supine position showed ground-glass opacities in the lower lobes, which disappeared (b) when the patient was placed in the prone position, proving that the ground-glass opacities were caused by gravity effects and insufficient inspiration.