Gustave Roussy Cancer Campus, F-94805, Villejuif, France; Laboratory of Immunomonitoring in Oncology, UMS 3655 CNRS/US 23 INSERM, Gustave Roussy Cancer Campus, F-94805, Villejuif, France; University Paris-Saclay, Faculty of Medicine, F-94270, Le Kremlin-Bicêtre, France.
Gustave Roussy Cancer Campus, F-94805, Villejuif, France; Laboratory of Immunomonitoring in Oncology, UMS 3655 CNRS/US 23 INSERM, Gustave Roussy Cancer Campus, F-94805, Villejuif, France; Department of Cancer Medicine, Gustave Roussy Cancer Campus, F-94805, Villejuif, France.
Eur J Cancer. 2019 Feb;108:88-96. doi: 10.1016/j.ejca.2018.12.017. Epub 2019 Jan 14.
Innate immunity represents the first step of activation of the immune system and dictates the quality of adaptive immune responses. Studies have reported links between systemic inflammatory or innate immune markers and prognosis in patients with lung cancer. To our knowledge, the prospective and concomitant study of these systemic markers has never been performed.
Advanced treatment-naive non-small cell lung cancer (NSCLC) patients eligible for first-line platinum-based chemotherapy were prospectively included from December 2012 to July 2015 (N = 148). Blood samples of patients were collected before the first cycle for fresh NK cell phenotyping. Peripheral blood mononuclear cells were cryopreserved for natural cytotoxicity receptor (NCR) genotyping as well as sera for NCR's ligand quantification. Data on leukocytes, neutrophils and monocyte counts and lactate dehydrogenase (LDH) levels were extracted from electronic medical records.
Among all studied markers, monocytosis, neutrophilia, leucocytosis, high LDH and sBAG6 levels and reduced levels of NCR3 transcripts were associated with poor overall survival (OS) in univariate analysis. The levels of NCR3 transcripts was linked to age, number of metastatic sites, monocyte counts, LDH and sBAG6 levels. Neutrophilia was associated to high sBAG6 levels. NCR3 was the unique innate immune parameter that remained as an independent factor associated with both OS (P = 0.003) and progression-free survival (P = 0.009) in the multivariate analysis.
This study brought evidence that these biomarkers are entangled; parameters associated with an inflammatory process were related to reduced levels of NCR3 transcripts. Finally, the level of NCR3 transcripts was independently associated with outcomes in treatment-naive patients with advanced NSCLC.
先天免疫代表免疫系统激活的第一步，并决定适应性免疫反应的质量。研究报告称，系统性炎症或先天免疫标志物与肺癌患者的预后之间存在关联。据我们所知，这些系统性标志物的前瞻性和伴随性研究从未进行过。
从 2012 年 12 月至 2015 年 7 月，前瞻性纳入了 148 名符合条件的初治晚期非小细胞肺癌（NSCLC）患者进行一线含铂化疗。在第一个周期前采集患者的血液样本，用于新鲜 NK 细胞表型分析。外周血单核细胞被冷冻保存，用于自然细胞毒性受体（NCR）的基因分型以及 NCR 配体的定量。从电子病历中提取白细胞、中性粒细胞和单核细胞计数以及乳酸脱氢酶（LDH）水平的数据。
在所有研究的标志物中，单核细胞增多症、中性粒细胞增多症、白细胞增多症、高 LDH 和 sBAG6 水平以及 NCR3 转录物水平降低与单因素分析中的总生存期（OS）不良相关。NCR3 转录物的水平与年龄、转移性病灶数量、单核细胞计数、LDH 和 sBAG6 水平相关。中性粒细胞增多症与高 sBAG6 水平相关。NCR3 是唯一与 OS（P=0.003）和无进展生存期（P=0.009）相关的独立因素的先天免疫参数。
这项研究提供了证据表明这些生物标志物是相互关联的；与炎症过程相关的参数与 NCR3 转录物水平降低有关。最后，NCR3 转录物水平与初治晚期 NSCLC 患者的结局独立相关。
