Jia Lin, Chen Naifei, Chen Xiao, Niu Chao, Liu Ziling, Ma Kewei, Yang Lei, Zhao Yuguang, Song Wei, Lu Jin, Chen Chen, Cong Xiaofeng, Wang Xu, Xu Yinghui, Cui Guozhen, Liu Zengguang, Chen Rongrong, Yin Huan, Zhang Na, Cui Jiuwei
Cancer center, The First Hospital of Jilin University, Changchun, China.
Department of Medical Center, Geneplus-Beijing Institute, Beijing, China.
Front Immunol. 2025 May 21;16:1595382. doi: 10.3389/fimmu.2025.1595382. eCollection 2025.
Combination strategies involving immune checkpoint inhibitors (ICIs) have been a prominent focus of research in the treatment of non-small cell lung cancer (NSCLC). Our prior findings demonstrated that the combination of autologous NK cells with the PD-1 antibody (Sintilimab), offered promising efficacy in NSCLC patients who failed the first-line platinum-based chemotherapy. Here, we present updated overall survival (OS) data from the final analysis, aiming to identify patient subgroups that derive maximal benefit from this therapeutic approach.
Twenty NSCLC patients without driver gene mutations were enrolled and treated with a combination of autologous NK cells and Sintilimab every three weeks. Multicolor immunofluorescence staining was applied to evaluate static markers within the tumor microenvironment. Concurrently, dynamic assessments were conducted using next-generation sequencing and monitoring of PD-1/PD-L1 expression on NK cells to identify patient populations with favorable prognoses.
The median OS was 27.3 months (95% CI, 0.76 to 53.8), with six patients still alive at the follow-up cutoff. A significant correlation was observed between the CD56+PD-L1+ cellular phenotype and extended survival. Clearance of circulating tumor DNA (ctDNA) and an increased percentage of PD-L1+ NK cells following treatment was associated with significantly better survival outcomes. Notably, prolonged treatment exposure did not lead to increased toxicity.
The combination of autologous NK cells with Sintilimab significantly enhances long-term survival in NSCLC patients without exacerbating adverse effects, presenting a promising strategy for future combination immunotherapy approaches in NSCLC treatment.
https://www.clinicaltrials.gov/ct2/show/NCT03958097, identifier NCT03958097.
涉及免疫检查点抑制剂（ICI）的联合策略一直是治疗非小细胞肺癌（NSCLC）研究的一个突出重点。我们之前的研究结果表明，自体NK细胞与PD-1抗体（信迪利单抗）联合使用，在一线铂类化疗失败的NSCLC患者中显示出有前景的疗效。在此，我们展示了最终分析的更新总生存期（OS）数据，旨在确定能从这种治疗方法中获得最大益处的患者亚组。
招募了20例无驱动基因突变的NSCLC患者，每三周接受一次自体NK细胞和信迪利单抗联合治疗。应用多色免疫荧光染色评估肿瘤微环境中的静态标志物。同时，使用下一代测序和监测NK细胞上PD-1/PD-L1的表达进行动态评估，以识别预后良好的患者群体。
中位OS为27.3个月（95%CI，0.76至53.8），随访截止时仍有6例患者存活。观察到CD56+PD-L1+细胞表型与生存期延长之间存在显著相关性。治疗后循环肿瘤DNA（ctDNA）的清除和PD-L1+NK细胞百分比的增加与显著更好的生存结果相关。值得注意的是，延长治疗时间并未导致毒性增加。
自体NK细胞与信迪利单抗联合使用可显著提高NSCLC患者的长期生存率，且不加重不良反应，为未来NSCLC治疗中的联合免疫治疗方法提供了一种有前景的策略。
https://www.clinicaltrials.gov/ct2/show/NCT03958097，标识符NCT03958097。
