The evolving landscape of immunotherapy in lung cancer: From mechanism to clinical translation

Background Lung cancer is the leading cause of cancer-related mortality worldwide, accounting for 12.4% of all incident cancers and 18.7% of total cancer deaths globally. Most patients are diagnosed at advanced stages, severely limiting curative options. Conventional therapies including surgery, chemotherapy, and targeted agents show reduced efficacy in advanced disease. Objective To critically evaluate the mechanistic basis, clinical efficacy, and translational barriers of immunotherapies (ICIs, cell therapies, vaccines, oncolytic viruses) in lung cancer. Methods A comprehensive literature review was conducted encompassing peer-reviewed publications, clinical trial registries, and regulatory databases, covering immune checkpoint inhibitors (ICIs), adoptive cellular therapies, cancer vaccines, bispecific antibodies, and oncolytic viruses in lung cancer management. Key Findings ICIs targeting PD-1/PD-L1 and CTLA-4 now constitute standard first-line therapy for advanced Non-Small Cell Lung Cancer (NSCLC) in appropriate patient subgroups. Adoptive cellular therapies, including CAR-T, TCR-T, and tumor-infiltrating lymphocyte (TIL) approaches, demonstrate early-phase feasibility, with Phase III validation pending. Personalized mRNA neoantigen vaccines are advancing toward pivotal Phase III endpoints in the adjuvant setting. Efficacy across modalities is constrained by the immunosuppressive tumor microenvironment (TME), resistance mechanisms, inter-patient heterogeneity, and immune-related adverse events. Conclusions Immunotherapy has fundamentally transformed the lung cancer treatment paradigm. Future priorities include multi-omics biomarker integration, rational combination strategies, mechanistic investigation of resistance pathways, and equitable global access to novel immunotherapeutic approaches.