背景:免疫检查点抑制剂,如抗程序性细胞死亡-1(PD-1)和PD-1配体-1(PD-L1)抗体,在提高肺癌长期生存率方面取得了突破性成果。尽管高水平的PD-L1表达和肿瘤突变负担已经成为关键的生物标志物,并非所有患者都能获得持久的益处,和抵抗免疫检查点封锁仍然是一个普遍的问题。了解肺癌的免疫学复杂性对于揭示控制对免疫调节治疗的反应和抗性的机制至关重要。本研究旨在探索外周免疫标志物在预测接受PD-1/PD-L1检查点抑制剂的肺癌患者治疗效率中的潜力。
方法:本研究纳入了71名接受PD-1/PD-L1抑制剂治疗的肺癌患者和20名健康对照。免疫细胞亚群(CD4+T细胞,CD8+T细胞,B细胞,NK细胞,和NKT细胞),T细胞和B细胞的表型分析,并进行了PMA/离子霉素刺激的淋巴细胞功能测定。
结果:肺癌患者表现出免疫细胞亚群的显著改变,Treg细胞百分比显著增加。后处理,CD3+T细胞的绝对数量大幅增加,CD8+T细胞,和NKT细胞,随着CD3+T和CD8+T细胞上HLA-DR的表达增加。完全缓解和非完全缓解(NCR)组之间的比较显示,NCR组中Treg细胞百分比和HLA-DRCD4T细胞百分比更高。
结论:研究结果表明,免疫细胞亚群和表型具有潜在的预测作用,特别是Treg细胞,HLA-DR+CD4+T细胞,和幼稚的CD4+T细胞,评估肺癌患者短期PD-1/PD-L1治疗疗效。这些见解为个性化治疗策略提供了宝贵的前景,并强调了免疫谱在肺癌免疫治疗中的重要性。
BACKGROUND: Immune checkpoint inhibitors, such as anti-programmed cell death-1 (PD-1) and PD-1 ligand-1 (PD-L1) antibodies, have achieved breakthrough results in improving long-term survival rates in lung cancer. Although high levels of PD-L1 expression and tumor mutational burden have emerged as pivotal biomarkers, not all patients derive lasting benefits, and resistance to immune checkpoint blockade remains a prevalent issue. Comprehending the immunological intricacies of lung cancer is crucial for uncovering the mechanisms that govern responses and resistance to immunomodulatory treatments. This study aimed to explore the potential of peripheral immune markers in predicting treatment efficiency among lung cancer patients undergoing PD-1/PD-L1 checkpoint inhibitors.
METHODS: This study enrolled 71 lung cancer patients undergoing PD-1/PD-L1 inhibitor therapy and 20 healthy controls. Immune cell subsets (CD4 + T cells, CD8 + T cells, B cells, NK cells, and NKT cells), phenotypic analysis of T cells and B cells, and PMA/Ionomycin-stimulated lymphocyte function assay were conducted.
RESULTS: Lung cancer patients exhibited significant alterations in immune cell subsets, notably an increased percentage of Treg cells. Post-treatment, there were substantial increases in absolute numbers of CD3 + T cells, CD8 + T cells, and NKT cells, along with heightened HLA-DR expression on CD3 + T and CD8 + T cells. Comparison between complete remission and non-complete remission (NCR) groups showed higher Treg cell percentages and HLA-DR + CD4 + T cells in the NCR group.
CONCLUSIONS: The study findings suggest potential predictive roles for immune cell subsets and phenotypes, particularly Treg cells, HLA-DR + CD4 + T cells, and naïve CD4 + T cells, in evaluating short-term PD-1/PD-L1 therapy efficacy for lung cancer patients. These insights offer valuable prospects for personalized treatment strategies and underscore the importance of immune profiling in lung cancer immunotherapy.