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PD-1 基因多态性对接受树突状细胞疫苗治疗的非小细胞肺癌的预后影响

英文原题:Prognostic Impact of PD-1 Polymorphisms in Non-small Cell Lung Cancer Receiving Dendritic Cell Vaccination.

PubMed 2025/10/01(内容时间) Anticancer Res Q4 · IF 1.8(JCR 2025)

研究概要

WT1和/或MUC1肽DC疫苗联合挽救性化疗似乎是晚期或复发NSCLC患者的一种有前景的治疗策略。PD-1 rs36084323 SNP与PNI被确定为独立预后因素,提示其可能作为生物标志物用于筛选适合该治疗方法的候选者。

研究思路结论见上方概要

非小细胞肺癌(NSCLC)患者的预后仍然较差。这项II期临床试验研究了使用Wilms瘤1(WT1)和/或黏蛋白1(MUC1)肽——通用肿瘤相关抗原——的树突状细胞(DC)疫苗联合化疗在晚期NSCLC患者中的疗效。此外,我们还检验了免疫检查点基因中的单核苷酸多态性(SNPs)是否可作为生存的预后标志物。

44例符合条件的转移性、不可切除或复发性NSCLC患者入组。DC每两至四周皮内注射一次,联合化疗。

第7次接种后,4例患者达到部分缓解,15例患者疾病稳定。自DC疫苗接种开始的中位PFS和OS分别为6.7个月和12.3个月。Log-rank分析显示,中性粒细胞与淋巴细胞比值、血小板与淋巴细胞比值、预后营养指数(PNI)和程序性细胞死亡1(PD-1)rs36084323 SNP均与PFS和OS显著相关。Cox回归分析确定PD-1 rs36084323 SNP和PNI是PFS和OS的独立预后因素。

展开英文摘要原文

BACKGROUND/AIM: The prognosis of patients with non-small cell lung cancer (NSCLC) remains poor. This phase II clinical trial investigated the efficacy of dendritic cell (DC) vaccination using Wilms' tumor 1 (WT1) and/or mucin 1 (MUC1) peptides - universal tumor-associated antigens - in combination with chemotherapy in patients with advanced-stage NSCLC. Additionally, we examined whether single nucleotide polymorphisms (SNPs) in immune checkpoint genes could serve as prognostic markers for survival. PATIENTS AND METHODS: Forty-four eligible patients with metastatic, unresectable or recurrent NSCLC were enrolled. DCs were administered intradermally every two to four weeks in combination with chemotherapy. RESULTS: Following the seventh vaccination, four patients achieved a partial response and 15 patients had stable disease. The median progression-free survival (PFS) and overall survival (OS) from the initiation of DC vaccination were 6.7 months and 12.3 months, respectively. Log-rank analysis revealed that neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, prognostic nutritional index (PNI) and the programmed cell death 1 (PD-1) rs36084323 SNP were significantly associated with both PFS and OS. Cox regression analysis identified the PD-1 rs36084323 SNP and PNI as independent prognostic factors for both PFS and OS. CONCLUSION: DC vaccination with WT1 and/or MUC1 peptides combined with salvage chemotherapy appears to be a promising treatment strategy for patients with advanced or relapsed NSCLC. The PD-1 rs36084323 SNP, along with PNI, was identified as an independent prognostic factor, suggesting its potential utility as a biomarker for selecting appropriate candidates for this treatment approach.

论文信息

作者
Ogasawara M、Miyashita M、Yamagishi Y、Ota S
单位
Department of Internal Medicine, Sapporo Hokuyu Hospital, Sapporo, Japan; ogasawara@hokuyu-aoth.org.Japan
文献类型
II 期临床试验
期刊
Anticancer research2025 Oct
原文标识
PubMed 41006036 · DOI 10.21873/anticanres.17780