Lung cancer immunotherapy in 2025: where we stand and what comes next?

Lung cancer continues to be the leading cause of cancer-related mortality worldwide, accounting for more deaths than breast, colorectal, and prostate cancers combined. Over the past decade, the introduction of immunotherapy has reshaped treatment paradigms, offering hope for long-term survival in a disease historically associated with dismal outcomes. The incorporation of immune checkpoint inhibitors (ICIs) into the treatment of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) has improved outcomes across early-stage, locally advanced, and metastatic settings. However, only a fraction of patients derive durable benefit, and challenges remain in overcoming resistance, predicting response, managing toxicity, and ensuring equitable access. This review provides a comprehensive overview of current progress in lung cancer immunotherapy. It discusses the immunobiology of lung tumors, the role of checkpoint blockade across disease stages, mechanisms of resistance, biomarker development, and combination strategies. Emerging modalities, including bispecific antibodies, CAR- and TCR-based cellular therapies, natural killer (NK) cell platforms, cytokine agonists, oncolytic viruses, and vaccines, are explored in depth. We also evaluate the translational significance of preclinical models, toxicity management, and issues of equity and accessibility. Finally, we outline key future directions that may redefine lung cancer immunotherapy in the coming years. Collectively, these advances highlight a transition from broad applications of checkpoint inhibition toward stage-specific, biomarker-driven, and multimodal immunotherapy approaches designed to convert temporary responses into durable remissions and, ultimately, cures.