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用于检测非小细胞肺癌中细胞组成、免疫格局、肿瘤及免疫相关标志物的体外分析方法的开发

Development of Ex Vivo Analysis for Examining Cell Composition, Immunological Landscape, Tumor and Immune Related Markers in Non-Small-Cell Lung Cancer.

作者信息

Ufimtseva Elena G, Gileva Margarita S, Kostenko Ruslan V, Kozlov Vadim V, Gulyaeva Lyudmila F

机构信息

Federal Research Center of Fundamental and Translational Medicine, 2 Timakova Street, 630060 Novosibirsk, Russia.

V. Zelman Institute for the Medicine and Psychology, Novosibirsk State University, 1 Pirogova Street, 630090 Novosibirsk, Russia.

出版信息

Cancers (Basel). 2024 Aug 20;16(16):2886. doi: 10.3390/cancers16162886.

DOI:10.3390/cancers16162886
PMID:39199657
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11352364/
Abstract

NSCLC is a very aggressive solid tumor, with a poor prognosis due to post-surgical recurrence. Analysis of the specific tumor and immune signatures of NSCLC samples is a critical step in prognostic evaluation and management decisions for patients after surgery. Routine histological assays have some limitations. Therefore, new diagnostic tools with the capability to quickly recognize NSCLC subtypes and correctly identify various markers are needed. We developed a technique for ex vivo isolation of cancer and immune cells from surgical tumor and lung tissue samples of patients with NSCLC (adenocarcinomas and squamous cell carcinomas) and their examination on ex vivo cell preparations and, parallelly, on histological sections after Romanovsky-Giemsa and immunofluorescent/immunochemical staining for cancer-specific and immune-related markers. As a result, PD-L1 expression was detected for some patients only by ex vivo analysis. Immune cell profiling in the tumor microenvironment revealed significant differences in the immunological landscapes between the patients' tumors, with smokers' macrophages with simultaneous expression of pro- and anti-inflammatory cytokines, neutrophils, and eosinophils being the dominant populations. The proposed ex vivo analysis may be used as an additional diagnostic tool for quick examination of cancer and immune cells in whole tumor samples and to avoid false negatives in histological assays.

摘要

非小细胞肺癌(NSCLC)是一种侵袭性很强的实体瘤,由于术后复发,预后较差。分析NSCLC样本的特定肿瘤和免疫特征是术后患者预后评估和管理决策的关键步骤。常规组织学检测存在一些局限性。因此,需要能够快速识别NSCLC亚型并正确鉴定各种标志物的新型诊断工具。我们开发了一种技术,用于从NSCLC患者(腺癌和鳞状细胞癌)的手术肿瘤和肺组织样本中体外分离癌细胞和免疫细胞,并对体外细胞制剂以及同时对经罗曼诺夫斯基-吉姆萨染色和免疫荧光/免疫化学染色检测癌症特异性和免疫相关标志物后的组织切片进行检查。结果发现,仅通过体外分析检测到部分患者的程序性死亡受体配体1(PD-L1)表达。肿瘤微环境中的免疫细胞图谱显示,患者肿瘤之间的免疫格局存在显著差异,同时表达促炎和抗炎细胞因子的吸烟者巨噬细胞、中性粒细胞和嗜酸性粒细胞是主要群体。所提出的体外分析可用作一种额外的诊断工具,用于快速检查整个肿瘤样本中的癌细胞和免疫细胞,并避免组织学检测中的假阴性结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/888b/11352364/2986aaa24538/cancers-16-02886-g006a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/888b/11352364/c5f1a39b5635/cancers-16-02886-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/888b/11352364/b6112f4a8df2/cancers-16-02886-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/888b/11352364/81abac5ba5e6/cancers-16-02886-g003a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/888b/11352364/5e4f469f71a0/cancers-16-02886-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/888b/11352364/d51576a6b469/cancers-16-02886-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/888b/11352364/2986aaa24538/cancers-16-02886-g006a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/888b/11352364/c5f1a39b5635/cancers-16-02886-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/888b/11352364/b6112f4a8df2/cancers-16-02886-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/888b/11352364/81abac5ba5e6/cancers-16-02886-g003a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/888b/11352364/5e4f469f71a0/cancers-16-02886-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/888b/11352364/d51576a6b469/cancers-16-02886-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/888b/11352364/2986aaa24538/cancers-16-02886-g006a.jpg

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本文引用的文献

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Mobocertinib in Patients with EGFR Exon 20 Insertion-Positive Non-Small Cell Lung Cancer (MOON): An International Real-World Safety and Efficacy Analysis.莫博赛替尼治疗 EGFR 外显子 20 插入阳性非小细胞肺癌患者(MOON):一项国际真实世界安全性和疗效分析。
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Cancer-associated fibroblast phenotypes are associated with patient outcome in non-small cell lung cancer.癌症相关成纤维细胞表型与非小细胞肺癌患者预后相关。
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