Zhang Liang, Li Ming-Jiang, Li Xiao-Ping, Yang Bo, Xiao Ting, Wang Ping, Zhang Wei-Dong
Department of Thoracic Surgery, Tianjin First Central Hospital, Tianjin 300190, P.R. China.
Department of Pharmacy, College of Pharmacy and Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, P.R. China.
Oncol Lett. 2025 Mar 26;29(5):251. doi: 10.3892/ol.2025.14997. eCollection 2025 May.
Despite advancements in immunotherapy, particularly regarding programmed cell death protein 1 (PD-1)/programmed death-ligand 1 blockades, the clinical outcomes in non-small cell lung cancer (NSCLC) remain variable with limited predictive biomarkers currently available. The present study investigated respiratory microbiota diversity as a potential biomarker to predict the efficacy of PD-1 blockades in patients with advanced NSCLC. A retrospective analysis was conducted on 60 patients treated with PD-1 blockades from May 2019 to May 2023. Clinical data were collected and respiratory microbiota from deep induced sputum specimens were analyzed using 16S rRNA gene sequencing. An index of respiratory microbiota α diversity was applied and exploratory analysis was performed accordingly. The objective response rate (ORR) and disease control rate among the 60 patients receiving PD-1 blockades was 23.3% (95% CI, 13.4-36.0%) and 58.3% (95% CI, 44.9-70.9%), respectively. Analysis of prognostic data of patients with advanced NSCLC receiving PD-1 blockades monotherapy demonstrated a median progression-free survival of 3.4 months (95% CI, 2.54-4.26) and a median overall survival (OS) of 12.3 months (95% CI, 6.29-18.31). Patients were stratified into high and low α diversity groups based on the Shannon diversity index of respiratory microbiota. The ORR was increased in the high diversity group (26.7%) compared with that of the low diversity group (20.0%), although the difference was not statistically significant (P=0.542). Notably, the high diversity group demonstrated a longer median PFS (3.9 vs. 2.8 months; P=0.017) and median OS (16.8 vs. 6.8 months; P=0.016) compared with that of the low diversity group. These findings suggested that PD-1 blockades demonstrate promising therapeutic activity for patients with previously treated advanced NSCLC in clinical practice. Respiratory microbiota α diversity might serve as a potential biomarker to predict the efficacy of PD-1 blockades monotherapy in patients with advanced NSCLC in the future. Therefore, further prospective studies are warranted to validate these findings and to explore the underlying mechanisms by which respiratory microbiota might modulate the immune response to cancer therapy.
尽管免疫疗法取得了进展，特别是在程序性细胞死亡蛋白1（PD-1）/程序性死亡配体1阻断方面，但非小细胞肺癌（NSCLC）的临床结果仍然存在差异，目前可用的预测生物标志物有限。本研究调查了呼吸道微生物群多样性作为预测晚期NSCLC患者PD-1阻断疗效的潜在生物标志物。对2019年5月至2023年5月接受PD-1阻断治疗的60例患者进行了回顾性分析。收集临床数据，并使用16S rRNA基因测序分析来自深度诱导痰标本的呼吸道微生物群。应用呼吸道微生物群α多样性指数并进行相应的探索性分析。60例接受PD-1阻断治疗的患者的客观缓解率（ORR）和疾病控制率分别为23.3%（95%CI，13.4-36.0%）和58.3%（95%CI，44.9-70.9%）。对接受PD-1阻断单药治疗的晚期NSCLC患者的预后数据进行分析，结果显示中位无进展生存期为3.4个月（95%CI，2.54-4.26），中位总生存期（OS）为12.3个月（95%CI，6.29-18.31）。根据呼吸道微生物群的香农多样性指数将患者分为高α多样性组和低α多样性组。高多样性组的ORR（26.7%）高于低多样性组（20.0%），尽管差异无统计学意义（P=0.542）。值得注意的是，与低多样性组相比，高多样性组的中位无进展生存期更长（3.9个月对2.8个月；P=0.017），中位总生存期更长（16.8个月对6.8个月；P=0.016）。这些发现表明，在临床实践中，PD-1阻断对先前治疗的晚期NSCLC患者显示出有前景的治疗活性。呼吸道微生物群α多样性可能作为预测未来晚期NSCLC患者PD-1阻断单药治疗疗效的潜在生物标志物。因此，有必要进行进一步的前瞻性研究来验证这些发现，并探索呼吸道微生物群可能调节对癌症治疗免疫反应的潜在机制。
