非小细胞肺癌免疫治疗生物标志物研究进展

Research Progress on Biomarkers for Immunotherapy of Non-Small Cell Lung Cancer

摘要: 非小细胞肺癌(non-small cell lung cancer, NSCLC)现在是全球发病率和死亡率最高的恶性肿瘤之一，约占肺癌总数的80%~85%。而免疫检查点抑制剂的出现(immune checkpoint inhibitors, ICIs)改变了NSCLC的治疗格局，它通过解除肿瘤免疫抑制、激活抗肿瘤免疫反应，显著改善了晚期患者预后，但仅20%~40%的患者能获得长期获益，且部分患者会出现严重免疫相关不良反应，这使疗效预测生物标志物成为精准治疗的关键。程序性死亡配体1 (PD-L1)表达与肿瘤突变负荷作为应用最广泛的标志物，其预测效能有限，难以满足个体化治疗需求。因此，寻找可靠的生物标志物，实现免疫治疗获益人群筛选、疗效评估及不良反应预测，成为当前研究热点。本文系统综述非小细胞肺癌免疫治疗生物标志物的研究进展。这些研究表明，整合多种生物标志物有望实现更精准的疗效预测，但如何优化组合策略并将其转化为临床实践仍是未来研究的重要方向。

Abstract: Non-small cell lung cancer (NSCLC) is currently one of the malignant tumors with the highest incidence and mortality worldwide, accounting for approximately 80%~85% of all lung cancer cases. The emergence of immune checkpoint inhibitors (ICIs) has revolutionized the therapeutic landscape of NSCLC. By relieving tumor immunosuppression and activating anti-tumor immune responses, ICIs have significantly improved the prognosis of patients with advanced NSCLC. However, only 20%~40% of patients can achieve long-term benefits, and some patients may experience severe immune-related adverse events, making predictive biomarkers the key to precision therapy. Programmed death-ligand 1 (PD-L1) expression and tumor mutational burden are the most widely used biomarkers, but their predictive efficacy is limited and cannot meet the needs of personalized treatment. Therefore, identifying reliable biomarkers for the selection of patients who benefit from immunotherapy, evaluation of therapeutic efficacy, and prediction of adverse reactions has become a hot topic in current research. This paper systematically reviews the research progress of biomarkers for immunotherapy in non-small cell lung cancer. These studies indicate that the integration of multiple biomarkers is expected to achieve more accurate prediction of therapeutic efficacy, but how to optimize combination strategies and translate them into clinical practice remains an important direction for future research.