Immune checkpoint inhibitor therapy‑related pneumonitis: How, when and why to diagnose and manage (Review)

Abstract

Immune checkpoint inhibitor (ICI) therapy has revolutionized cancer treatment by enhancing the immune response against tumor cells. However, their influence on immune pathways can lead to immune-related adverse events such as pneumonitis, necessitating rapid diagnosis and management to prevent severe complications. These adverse events arise from the activation of the immune system by immunotherapeutic drugs, leading to immune-mediated inflammation and tissue damage in various organs and tissues throughout the body. The present review article discusses the pathophysiology, clinical presentation, diagnostic modalities and management strategies for ICI-related pneumonitis, emphasizing early recognition and tailored interventions. Future research endeavors should focus on elucidating the underlying mechanisms of pneumonitis and identifying predictive biomarkers to guide personalized treatment strategies in this evolving field of oncology.

Keywords: adverse events; diagnosis; immune checkpoint inhibitors; management; pneumonitis.

Figure 1

Outline of the pathophysiological mechanisms of ICI-related pneumonitis. The pathogenesis of immune-related adverse events seems linked to the disruption of immune regulation of tissue homeostasis rather than the activation of the immune system, as suggested by the lack of laboratory confirmation of autoimmunity. ICI, immune checkpoint inhibitor; Treg cell, T-regulatory cell; Th1 cell, type 1 T-helper cell; CCL17, C-C motif chemokine ligand 17.

Figure 2

(A) Axial and (B) coronal CT scan with lung parenchyma reconstruction demonstrating consolidation in the left lower lobe characterized by air bronchograms (see arrows). The image is from a 52-year-old patient undergoing therapy with nivolumab for locally advanced gastric cancer.

Figure 3

(A) Axial and (B) coronal CT scans with lung parenchyma reconstruction revealed extensive ground-glass opacity predominantly distributed peripherally in the lower lung lobes, accompanied by interstitial septal thickening and more consolidated regions (see arrows). The consolidations are notably pronounced and extensive in the right lower lobe, confirming immunotherapy-induced pneumonia in a 58-year-old patient recently diagnosed with lung adenocarcinoma and undergoing osimertinib therapy.

Figure 4

(A) Axial and (B) coronal CT scan with lung parenchyma reconstruction depicting a 58-year-old female patient with metastatic rectal adenocarcinoma with progressing pulmonary metastases undergoing experimental immunotherapy with Nivolumab (see white arrows). Note several areas of increased parenchymal density, predominantly perilesional, characterized by ground-glass opacity (see orange arrows).