Advances in neoadjuvant immunotherapy for non-small cell lung cancer

Non-small cell lung cancer (NSCLC) represents the majority of lung cancer cases and remains a leading cause of cancer-related mortality worldwide. Early-stage NSCLC is primarily treated with surgical resection; however, high recurrence and metastasis rates necessitate additional therapies. Emerging neoadjuvant immunotherapy, particularly immune checkpoint inhibitors (ICIs), has demonstrated efficacy in enhancing anti-tumor immune responses by restoring CD8⁺ T cell activity and promoting tumor-specific cytotoxicity. Preclinical studies indicate that combination strategies, including dual PD-1/CTLA-4 blockade, oncolytic viral therapy, and chemoimmunotherapy, synergistically improve survival and pathological response. Clinical trials have confirmed the safety and feasibility of these approaches, with neoadjuvant ICIs achieving major pathological response (MPR) and pathological complete response (pCR) in a substantial proportion of operable NSCLC patients. Predictive biomarkers, including PD-L1, tumor mutational burden (TMB), circulating tumor DNA (ctDNA), and immune profiling, may guide patient selection and optimize treatment outcomes. This review summarizes current evidence on the mechanisms, clinical efficacy, and biomarker-driven strategies for neoadjuvant immunotherapy in NSCLC, highlighting its potential to improve long-term survival and inform personalized therapeutic approaches.