Arrieta Oscar, Montes-Servín Edgar, Hernandez-Martinez Juan-Manuel, Cardona Andrés F, Casas-Ruiz Eibar, Crispín José C, Motola Daniel, Flores-Estrada Diana, Barrera Lourdes
Functional Unit of Thoracic Oncology and Laboratory of Personalized Medicine, Instituto Nacional de Cancerología, Mexico City, Mexico.
CONACyT-Instituto Nacional de Cancerología, Mexico City, Mexico.
Oncotarget. 2017 Oct 24;8(60):101994-102005. doi: 10.18632/oncotarget.22025. eCollection 2017 Nov 24.
Binding of programmed death-1 (PD-1) with its ligands (PD-L1/2) transmits a co-inhibitory signal in activated T-cells that promotes T-cell exhaustion, leading to tumor immune evasion. The efficacy of antibodies targeting PD-1 and PD-L1 has led to a paradigm shift in lung cancer treatment but the prognostic and predictive value of tumor PD-L1 expression remains controversial. Evaluating PD-1, PD-L1/2 expression in peripheral blood cells may serve as a potential biomarker for prognosis and response to therapy. In this prospective observational study, plasma cytokine levels and PD-1, PD-L1 and PD-L2 expression was evaluated in circulating CD3, CD3CD4 and CD3CD8 cells from 70 treatment-naïve patients with advanced NSCLC (Stage IIIB and IV) and from 10 healthy donors. The primary objective was to assess OS according to PD-1, PD-L1, PD-L2 expression status on PBMCs and lymphocyte subsets. Our results indicate that the percentage of PD-L1CD3, PD-L1CD3CD8 PD-L2PBMCs, PD-L2CD3, PD-L2CD3CD4 cells was higher in patients than in healthy donors. Survival was decreased among patients with a high percentage of either PD-1PBMCs, PD-1CD3, PD-L1CD3, PD-L1CD3CD8, PD-L2CD3, PD-L2CD3CD4, or PD-L2CD3CD8 cells. IL-2 and TNF-α showed the strongest association with PD-L1 and PD-L2 expression on specific subsets of T-lymphocytes. Our findings suggest that increased PD-1/PD-L1/PDL-2 expression in PBMCs, particularly in T-cells, may be an additional mechanism leading to tumor escape from immune control. This study is registered with ClinicalTrials.gov, number NCT02758314.
程序性死亡蛋白 1（PD-1）与其配体（PD-L1/2）结合会在活化的 T 细胞中传递共抑制信号，促进 T 细胞耗竭，从而导致肿瘤免疫逃逸。靶向 PD-1 和 PD-L1 的抗体的疗效已导致肺癌治疗发生了范式转变，但肿瘤 PD-L1 表达的预后和预测价值仍存在争议。评估外周血细胞中 PD-1、PD-L1/2 的表达可能作为预后和治疗反应的潜在生物标志物。在这项前瞻性观察研究中，对 70 例未经治疗的晚期非小细胞肺癌（IIIB 期和 IV 期）患者以及 10 名健康供体的循环 CD3、CD3CD4 和 CD3CD8 细胞中的血浆细胞因子水平以及 PD-1、PD-L1 和 PD-L2 表达进行了评估。主要目的是根据 PBMC 和淋巴细胞亚群上的 PD-1、PD-L1、PD-L2 表达状态评估总生存期（OS）。我们的结果表明，患者中 PD-L1CD3、PD-L1CD3CD8、PD-L2PBMCs、PD-L2CD3、PD-L2CD3CD4 细胞的百分比高于健康供体。在 PD-1PBMCs、PD-1CD3、PD-L1CD3、PD-L1CD3CD8、PD-L2CD3、PD-L2CD3CD4 或 PD-L2CD3CD8 细胞百分比高的患者中，生存率降低。白细胞介素-2（IL-2）和肿瘤坏死因子-α（TNF-α）与 T 淋巴细胞特定亚群上的 PD-L1 和 PD-L2 表达显示出最强的关联。我们的研究结果表明，PBMC 中，特别是 T 细胞中 PD-1/PD-L1/PDL-2 表达增加可能是导致肿瘤逃避免疫控制的另一种机制。本研究已在 ClinicalTrials.gov 注册，注册号为 NCT02758314。
Zotero 插件