Immune-related adverse events in non-small cell lung cancer: Occurrence, mechanisms and therapeutic strategies

The emergence of immune checkpoint inhibitors (ICIs) has heralded a transformative era in the therapeutic landscape of non-small cell lung cancer (NSCLC). While ICIs have demonstrated clinical efficacy in a portion of patients with NSCLC, these treatments concurrently precipitate a spectrum of immune-related adverse events (irAEs), encompassing mild to severe manifestations, collectively posing a risk of significant organ damage. Consequently, there exists an imperative to augment our comprehension of the pathophysiological underpinnings of irAEs and to formulate more efficacious preventive and ameliorative strategies. In this comprehensive review, we delineate the clinical presentation of organ-specific irAEs in patients with NSCLC and provide an in-depth analysis of recent advancements in understanding the mechanisms driving ICI-induced toxicity. Furthermore, we discuss potential strategies and targets for ameliorating these irAEs. Ultimately, this review aims to furnish valuable insights to guide further research endeavours in the context of irAEs in NSCLC patients. Immunotherapy not only revolutionises lung cancer treatment but also poses serious toxicity risks. Elucidating irAE mechanisms in NSCLC: T/B-cell dysregulation, cytokine imbalances, autoantibody production, genetic predispositions and gut microbiome alterations. Highlighting precise irAE interventions in NSCLC: corticosteroids, targeted immunosuppressants, monoclonal antibodies targeting lymphocytes, cytokine inhibitors and signalling pathway modulators. image