文章：

基因表达与高淋巴细胞计数或可预测晚期非小细胞肺癌患者接受免疫检查点抑制剂治疗的持久临床获益

Gene Expressions and High Lymphocyte Count May Predict Durable Clinical Benefits in Patients with Advanced Non-Small-Cell Lung Cancer Treated with Immune Checkpoint Inhibitors

原文发布日期：8 September 2023

DOI: 10.3390/cancers15184480

类型: Article

开放获取: 是

英文摘要：

Background: Not all patients with advanced non-small cell lung cancer (NSCLC) benefit from immune checkpoint inhibitors (ICIs). Therefore, we aimed to assess the predictive potential of gene expression profiling (GEP), peripheral immune cell counts, and clinical characteristics. Methods: The primary endpoint of this prospective, observational study was a durable clinical benefit (DCB) defined as progression-free survival >6 months. In a subgroup with histological biopsies of sufficient quality (n= 25), GEP was performed using the nCounter®PanCancer IO 360 panel. Results: DCB was observed in 49% of 123 included patients. High absolute lymphocyte count (ALC) and absence of liver metastases were associated with DCB (OR = 1.95,p= 0.038 and OR = 0.36,p= 0.046, respectively). GEP showed clustering of differentially expressed genes according to DCB, and a strong association between PD-L1 assessed by GEP (CD274) and immunohistochemistry (IHC) was observed (p= 0.00013). The TGF-β, dendritic cell, and myeloid signature scores were higher for patients without DCB, whereas the JAK/STAT loss signature scores were higher for patients with DCB (unadjustedp-values < 0.05). Conclusions: ALC above 1.01 × 109/L and absence of liver metastases were significantly associated with DCB in ICI-treated patients with NSCLC. GEP was only feasible in 20% of the patients. GEP-derived signatures may be associated with clinical outcomes, and PD-L1 could be assessed by GEP rather than IHC.

摘要翻译： 

背景：并非所有晚期非小细胞肺癌（NSCLC）患者均能从免疫检查点抑制剂（ICIs）治疗中获益。本研究旨在评估基因表达谱（GEP）、外周免疫细胞计数及临床特征的预测潜力。方法：本前瞻性观察性研究的主要终点定义为持续临床获益（DCB），即无进展生存期超过6个月。在组织活检样本质量符合要求的亚组（n=25）中，采用nCounter® PanCancer IO 360检测面板进行GEP分析。结果：在纳入的123例患者中，49%观察到DCB。高绝对淋巴细胞计数（ALC）和无肝转移与DCB显著相关（比值比分别为1.95，p=0.038和0.36，p=0.046）。GEP分析显示差异表达基因根据DCB状态呈现聚类特征，且GEP评估的PD-L1（CD274）与免疫组化（IHC）检测结果具有强相关性（p=0.00013）。未获得DCB患者的TGF-β信号通路、树突状细胞和髓系特征评分较高，而获得DCB患者的JAK/STAT缺失特征评分较高（未经校正p值<0.05）。结论：在接受ICI治疗的NSCLC患者中，ALC高于1.01×10⁹/L且无肝转移与DCB显著相关。GEP检测仅在20%患者中具有可行性。GEP衍生的特征谱可能与临床结局相关，且PD-L1可通过GEP而非IHC进行评估。

原文链接：

Gene Expressions and High Lymphocyte Count May Predict Durable Clinical Benefits in Patients with Advanced Non-Small-Cell Lung Cancer Treated with Immune Checkpoint Inhibitors