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术后靶向免疫治疗对肺癌患者外周血细胞因子及免疫细胞谱的影响。

The effects of postoperative targeted immunotherapy on peripheral blood cytokines and immune cell profile in lung cancer patients.

作者信息

Zhang Chuang, Mo Hongmei, Li Min, Wang Shuaiyan, Dou Xiaowen, Zhang Xiuming

机构信息

School of Medicine, Anhui University of Science and Technology, Huainan, China.

Medical Laboratory of the Third Affiliated Hospital of Shenzhen University, Shenzhen, China.

出版信息

Front Oncol. 2024 Jun 5;14:1342624. doi: 10.3389/fonc.2024.1342624. eCollection 2024.

Abstract

OBJECTIVE

Cytokines and cell subsets are important components of the tumor microenvironment. Previous research has revealed that there are differences in cytokines and cell subsets in the peripheral blood of lung cancer (LCA) patients before and after eradication. The purpose of this study is to explore the monitoring value of cytokines and cellular subpopulations as biomarkers in post-immunotherapy monitoring of patients with LCA after surgery.

METHODS

We conducted a case-control study using double-antibody sandwich magnetic microsphere flow cytometry with immunofluorescence technology and fluorescent monoclonal antibody multiparameter flow cytometry to detect differences in peripheral blood cytokines and cell subsets between LCA patients after immunotherapy and healthy controls.

RESULTS

Our research results show that there are differences in the levels of IL-4, IL-6, IL-10, IL-17, IFN-γ, TNF-α in the peripheral blood of LCA patients (n=70) after immunotherapy compared to the healthy controls (n=55) (), and there are differences in 10 cell subgroups including DP T Cells, AT cells, and NLR in the peripheral blood compared to the healthy controls (n=35) (). Further analysis revealed significant differences in the detection data of IL-6, IL-10, IFN-γ, CD56 NK cells, Total B cells, Total NE cells, CD15M cells, and NLR between LCA deceased patients (n=25) and LCA surviving patients (n=27) during the same period (). The continuous monitoring of cytokines and cell subsets is far more valuable than a single-time test, as abnormal fluctuations in the data of cytokines and cell subsets are often associated with poor prognosis. In addition, IL-6 and NLR showed the strongest discriminative ability between postoperative immunotherapy-treated LCA patients and healthy controls, with AUC values of 0.840 and 0.822, respectively. There was a significant association between IFN-γ and distant metastasis in LCA (), as well as between CD56 NK cells and lymph node infiltration ().

CONCLUSION

This research results support peripheral blood cytokines and cell subsets as biomarkers for monitoring the postoperative immune status and predicting the prognosis of LCA patients after immunotherapy. The continuous monitoring of cytokines and cell subsets is far more valuable than a single-time detection.

摘要

目的

细胞因子和细胞亚群是肿瘤微环境的重要组成部分。既往研究表明,肺癌(LCA)患者根除前后外周血中的细胞因子和细胞亚群存在差异。本研究旨在探讨细胞因子和细胞亚群作为生物标志物在LCA患者术后免疫治疗监测中的价值。

方法

我们采用双抗体夹心磁微球流式细胞术结合免疫荧光技术以及荧光单克隆抗体多参数流式细胞术进行病例对照研究,以检测免疫治疗后LCA患者与健康对照外周血细胞因子和细胞亚群的差异。

结果

我们的研究结果显示,与健康对照(n = 55)相比,免疫治疗后LCA患者(n = 70)外周血中IL-4、IL-6、IL-10、IL-17、IFN-γ、TNF-α水平存在差异(),与健康对照(n = 35)相比,外周血中包括双阳性T细胞、AT细胞和NLR在内的10个细胞亚群存在差异()。进一步分析显示,同期LCA死亡患者(n = 25)和LCA存活患者(n = 27)之间,IL-6、IL-10、IFN-γ、CD56自然杀伤细胞、总B细胞、总中性粒细胞、CD15M细胞和NLR的检测数据存在显著差异()。细胞因子和细胞亚群数据的连续监测远比单次检测更有价值,因为细胞因子和细胞亚群数据的异常波动往往与预后不良相关。此外,IL-6和NLR在术后免疫治疗的LCA患者与健康对照之间显示出最强的鉴别能力,AUC值分别为0.840和0.822。LCA中IFN-γ与远处转移之间存在显著关联(),以及CD56自然杀伤细胞与淋巴结浸润之间存在显著关联()。

结论

本研究结果支持外周血细胞因子和细胞亚群作为监测LCA患者术后免疫状态及预测免疫治疗后预后的生物标志物。细胞因子和细胞亚群的连续监测远比单次检测更有价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5345/11188683/c7687e805eaf/fonc-14-1342624-g001.jpg

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