The advent of immune checkpoint inhibitors (ICIs), for instance, programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) blockers, has greatly improved the outcome of patients affected by non-small cell lung cancer (NSCLC). However, most NSCLC patients either do not respond to ICI monotherapy or develop resistance to it after an initial response. Therefore, the identification of biomarkers for predicting the response of patients to ICI monotherapy represents an urgent issue. Great efforts are currently dedicated toward identifying blood-based biomarkers to predict responses to ICI monotherapy. In this study, more commonly utilized blood-based biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR) and the lung immune prognostic index (LIPI) score, as well as the frequency/number and activation status of various types of circulating innate immune cell populations, were evaluated in NSCLC patients at baseline before therapy initiation. The data indicated that, among all the parameters tested, low plasmacytoid dendritic cell (pDC), slan+-monocyte and natural killer cell counts, as well as a high LIPI score and elevated PD-L1 expression levels on type 1 conventional DCs (cDC1s), were independently correlated with a negative response to ICI therapy in NSCLC patients. The results from this study suggest that the evaluation of innate immune cell numbers and phenotypes may provide novel and promising predictive biomarkers for ICI monotherapy in NSCLC patients.
以程序性细胞死亡蛋白1（PD-1）/PD-1配体1（PD-L1）抑制剂为代表的免疫检查点抑制剂的出现，显著改善了非小细胞肺癌患者的临床预后。然而，多数患者对单药免疫治疗缺乏应答或在初始应答后产生耐药性。因此，寻找能够预测患者对单药免疫治疗反应的生物标志物成为亟待解决的关键问题。目前研究重点聚焦于探索基于血液的生物标志物。本研究在非小细胞肺癌患者治疗前基线期，评估了临床常用血液标志物（中性粒细胞-淋巴细胞比值、肺免疫预后指数评分）及各类循环先天免疫细胞亚群的频率/数量与活化状态。数据显示，在所有检测参数中，浆细胞样树突状细胞、slan+单核细胞与自然杀伤细胞计数偏低，肺免疫预后指数评分偏高，以及1型经典树突状细胞表面PD-L1表达水平升高，均与非小细胞肺癌患者对免疫检查点抑制剂治疗无应答独立相关。本研究提示，对先天免疫细胞数量及表型的评估可能为预测非小细胞肺癌患者单药免疫治疗反应提供新型且具有前景的生物标志物。
肿瘤(癌症)患者之家