Integration of immunogenic cell death in the treatment landscape of non-small cell lung cancer: harnessing the power of the immune system

Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases and is one of the leading causes of cancer-related death worldwide. Although traditional therapies such as chemotherapy, radiotherapy and molecular targeted therapy, as well as immunotherapy, have made substantial progress, drug resistance and tumour recurrence remain significant challenges. Immunogenic cell death (ICD), a special type of cell death, has emerged as a cutting-edge strategy for NSCLC treatment due to its unique immune activation mechanism. ICD orchestrates immunogenic tumour cell death via coordinated endoplasmic reticulum stress and reactive oxygen species generation, resulting in the release of damage-associated molecular patterns (DAMPs). Through a synergistic mechanism, tumour-associated antigens are unveiled, antigen-presenting cells such as dendritic cells are activated, and T cell responses targeting tumour-specific antigens are triggered. These factors collectively act to reprogramme the immunosuppressive tumour microenvironment (TME). Preclinical trials have demonstrated that chemotherapy, radiotherapy and molecular targeted therapy enhance the antitumour effect by inducing ICD, providing new strategies for treating NSCLC. This review systematically summarises the induction strategies of ICD in the treatment of NSCLC and focuses on the progress in preclinical experiments and clinical trials. Additionally, the current paper discusses the core challenges and future development directions of ICD in NSCLC therapy, to provide novel insights into the optimised utilisation and clinical implementation of ICD induction strategies.