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免疫细胞图谱在未经治疗的肺鳞癌和腺癌中的研究。

Immune cell landscape in therapy-naïve squamous cell and adenocarcinomas of the lung.

机构信息

Institute of Pathology, Medical University of Graz, Neue Stiftingtalstrasse 6, 8010, Graz, Austria.

Division of Oncology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria.

出版信息

Virchows Arch. 2018 Apr;472(4):589-598. doi: 10.1007/s00428-018-2326-0. Epub 2018 Mar 8.

Abstract

Squamous cell and adenocarcinomas of the lung develop different mechanisms during carcinogenesis to evade attacks of the immune system. Besides the well-known check-point control programmed death 1 and its ligand, many more mechanisms, acting either tumoricidal or in favor of tumor progression, exist. Analysis of the immune cell profiles in resected tissues and bronchoalveolar lavage samples and correlation between them and with overall survival data was performed. In all tumor samples in this study, cells of the immune system expressed a tumor-cooperating phenotype. High numbers of regulatory T cells, or alternatively expression of Vista on lymphocytes was present. Tumoricidal dendritic cells were absent in tumor tissue, and barely present in bronchoalveolar lavage, whereas tumor-friendly monocytoid and plasmocytoid dendritic cells were seen in both. Alveolar macrophages were predominantly differentiated into tumor-cooperating M2 types, whereas tumoricidal M1 macrophages were absent or rare. The expression of PDL1 on tumor cells did not correlate with any other immune cells. Expression of PD1 on lymphocytes was frequently encountered. None of analyzed immune cells showed correlation with overall survival. Immune cells in bronchoalveolar lavage and tissue did not correlate. For the first time, a tissue-based analysis of different immune cells in squamous cell and adenocarcinomas of the lung is provided, trying to explain their potential role in tumor development and progression. Discordant numbers of cells with bronchoalveolar lavage are most probably due to the fact that bronchoalveolar lavage reflects the situation in the whole lung, where chronic obstructive lung disease and other conditions are present.

摘要

肺的鳞状细胞癌和腺癌在癌变过程中发展出不同的机制,以逃避免疫系统的攻击。除了众所周知的检查点控制程序性死亡 1 及其配体外,还有许多机制,既有杀瘤作用,也有利于肿瘤进展。分析了切除组织和支气管肺泡灌洗液样本中的免疫细胞谱,并将其与总体生存数据相关联。在本研究的所有肿瘤样本中,免疫系统的细胞均表现出肿瘤协同表型。调节性 T 细胞数量较多,或者淋巴细胞上表达 Vista。肿瘤杀伤性树突状细胞在肿瘤组织中缺失,在支气管肺泡灌洗液中几乎不存在,而肿瘤友好型单核细胞样和浆细胞样树突状细胞在两者中均可见。肺泡巨噬细胞主要分化为肿瘤协同 M2 型,而肿瘤杀伤性 M1 巨噬细胞缺失或罕见。肿瘤细胞上 PDL1 的表达与任何其他免疫细胞均无关。淋巴细胞上 PD1 的表达经常出现。分析的免疫细胞均与总生存率无关。支气管肺泡灌洗液和组织中的免疫细胞无相关性。这是首次对肺的鳞状细胞癌和腺癌中的不同免疫细胞进行基于组织的分析,试图解释它们在肿瘤发展和进展中的潜在作用。支气管肺泡灌洗液中细胞数量的差异很可能是由于支气管肺泡灌洗反映了整个肺部的情况,而慢性阻塞性肺疾病和其他情况也存在于整个肺部。

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