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头颈癌中引流肿瘤淋巴结的中性粒细胞的表型差异

Phenotypical differences of neutrophils patrolling tumour-draining lymph nodes in head and neck cancer.

作者信息

Ekstedt Sandra, Piersiala Krzysztof, Kolev Aeneas, Farrajota Neves da Silva Pedro, Margolin Gregori, Kumlien Georén Susanna, Cardell Lars-Olaf

机构信息

Division of ENT Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.

Department of Otorhinolaryngology, Karolinska University Hospital, Stockholm, Sweden.

出版信息

Br J Cancer. 2024 Dec;131(12):1893-1900. doi: 10.1038/s41416-024-02891-5. Epub 2024 Nov 14.

DOI:10.1038/s41416-024-02891-5
PMID:39543389
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11628601/
Abstract

BACKGROUND

The complexity and heterogeneity of neutrophils are recognized, especially their roles in modulating inflammation and cancer immune responses. The detailed functions of neutrophils in human tumour-draining lymph nodes (TDLNs), specifically in the context of head and neck cancer, remain inadequately characterized.

AIM

This study aims to delineate the phenotypic diversity of neutrophils in TDLNs, non-tumour-draining lymph nodes (nTDLNs) from patients with oral squamous cell carcinoma (OSCC), and to evaluate their correlation with clinical outcomes.

METHODS

A flow cytometry-based investigation.

RESULTS

Neutrophils manifest a tissue-specific heterogeneity with significant phenotypic differences between compartments. A substantial fraction of neutrophils displayed an activated CD16CD62L profile in TDLNs, more prominent in patients with advanced T stages, implicating their involvement in the disease's progression. Notably, the presence of this activated neutrophil phenotype in TDLNs was strongly associated with poorer patient prognosis.

CONCLUSIONS

The study confirms the heterogeneity of neutrophils in human TDLNs, aligning with findings from animal models but extending them to show clinical relevance in human disease. The correlation of neutrophil phenotypes with cancer progression and prognosis emphasizes the importance of these cells in the tumour-microenvironment. The data suggests a future possibility to develop targeted therapies that modulate the neutrophilic response in OSCC.

摘要

背景

中性粒细胞的复杂性和异质性已得到公认,尤其是它们在调节炎症和癌症免疫反应中的作用。中性粒细胞在人类肿瘤引流淋巴结(TDLN)中的详细功能,特别是在头颈部癌症背景下,仍未得到充分描述。

目的

本研究旨在描绘口腔鳞状细胞癌(OSCC)患者的肿瘤引流淋巴结(TDLN)和非肿瘤引流淋巴结(nTDLN)中中性粒细胞的表型多样性,并评估它们与临床结局的相关性。

方法

基于流式细胞术的研究。

结果

中性粒细胞表现出组织特异性异质性,各区域之间存在显著的表型差异。在TDLN中,相当一部分中性粒细胞呈现活化的CD16CD62L表型,在T分期较晚的患者中更为明显,这表明它们参与了疾病的进展。值得注意的是,TDLN中这种活化的中性粒细胞表型的存在与患者预后较差密切相关。

结论

该研究证实了人类TDLN中中性粒细胞的异质性,与动物模型的研究结果一致,但将其扩展以显示在人类疾病中的临床相关性。中性粒细胞表型与癌症进展和预后的相关性强调了这些细胞在肿瘤微环境中的重要性。数据提示未来有可能开发出调节OSCC中性粒细胞反应的靶向治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d40/11628601/20127baf3c0c/41416_2024_2891_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d40/11628601/cc8430a55cac/41416_2024_2891_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d40/11628601/8e1c61e3595a/41416_2024_2891_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d40/11628601/90d03a964190/41416_2024_2891_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d40/11628601/20127baf3c0c/41416_2024_2891_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d40/11628601/cc8430a55cac/41416_2024_2891_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d40/11628601/8e1c61e3595a/41416_2024_2891_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d40/11628601/90d03a964190/41416_2024_2891_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d40/11628601/20127baf3c0c/41416_2024_2891_Fig4_HTML.jpg

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本文引用的文献

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Cell Rep. 2022 Aug 16;40(7):111171. doi: 10.1016/j.celrep.2022.111171.
2
Tumor-associated neutrophils (TANs) in human carcinoma-draining lymph nodes: a novel TAN compartment.人类癌引流淋巴结中的肿瘤相关中性粒细胞(TANs):一个新的TAN区室。
Clin Transl Immunology. 2021 Feb 16;10(2):e1252. doi: 10.1002/cti2.1252. eCollection 2021.
3
Phenotypically distinct neutrophils patrol uninfected human and mouse lymph nodes.
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Sci Rep. 2025 Feb 21;15(1):6313. doi: 10.1038/s41598-025-90237-3.
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Proc Natl Acad Sci U S A. 2019 Sep 17;116(38):19083-19089. doi: 10.1073/pnas.1905054116. Epub 2019 Sep 4.
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