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头颈部鳞状细胞癌的高维解构揭示了与预后和治疗反应相关的临床上不同的细胞状态和生态系统。

High-dimensional deconstruction of HNSC reveals clinically distinct cellular states and ecosystems that are associated with prognosis and therapy response.

作者信息

Xiao Lei, Shen Zhe, Pan Zhaoyu, Qiu Yuanzheng, Huang Donghai, Liu Yong, Liu Chao, Zhang Xin

机构信息

Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, China.

Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Changsha, 410008, Hunan, China.

出版信息

J Transl Med. 2025 Mar 1;23(1):254. doi: 10.1186/s12967-025-06299-4.

DOI:10.1186/s12967-025-06299-4
PMID:40025504
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11872339/
Abstract

BACKGROUND

Characterizing the variety of cell types in the tumor microenvironment (TME) and their organization into cellular communities is vital for elucidating the biological diversity of cancer and informing therapeutic strategies.

METHODS

Here, we employed a machine learning-based algorithm framework, EcoTyper, to analyze single-cell transcriptomes from 139 patients with head and neck squamous cell carcinoma (HNSC)and gene expression profiles from 983 additional HNSC patients, aiming to delineate the fundamental cell states and ecosystems integral to HNSC.

RESULTS

A diverse landscape of 66 cell states and 9 ecosystems within the HNSC microenvironment was identified, revealing classical cell types while also expanding upon previous immune classifications. Survival analysis revealed that specific cell states and ecotypes (ecosystems) are associated with patient prognosis, underscoring their potential as indicators of clinical outcomes. Moreover, distinct cell states and ecotypes exhibited varying responses to immunotherapy and chemotherapy, with several showing promise as predictive biomarkers for treatment efficacy.

CONCLUSION

Our large-scale integrative transcriptome analysis provides high-resolution insights into the cellular states and ecosystems of HNSC, facilitating the discovery of novel biomarkers and supporting the development of precision therapies.

摘要

背景

表征肿瘤微环境(TME)中细胞类型的多样性及其组成细胞群落的方式,对于阐明癌症的生物多样性和指导治疗策略至关重要。

方法

在此,我们采用了一种基于机器学习的算法框架EcoTyper,来分析139例头颈部鳞状细胞癌(HNSC)患者的单细胞转录组以及另外983例HNSC患者的基因表达谱,旨在描绘出HNSC所特有的基本细胞状态和生态系统。

结果

在HNSC微环境中识别出了由66种细胞状态和9种生态系统构成的多样格局,揭示了经典细胞类型,同时也扩展了以往的免疫分类。生存分析表明,特定的细胞状态和生态型(生态系统)与患者预后相关,突显了它们作为临床结果指标的潜力。此外,不同的细胞状态和生态型对免疫疗法和化疗表现出不同的反应,其中几种显示出有望成为治疗疗效的预测生物标志物。

结论

我们的大规模综合转录组分析为HNSC的细胞状态和生态系统提供了高分辨率的见解,有助于发现新的生物标志物并支持精准疗法的开发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4918/11872339/9f87e4a4e49b/12967_2025_6299_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4918/11872339/31646f6e42b6/12967_2025_6299_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4918/11872339/ea2abd50b151/12967_2025_6299_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4918/11872339/4f039eb5100c/12967_2025_6299_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4918/11872339/753035024f34/12967_2025_6299_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4918/11872339/0c89026b4fd2/12967_2025_6299_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4918/11872339/9f87e4a4e49b/12967_2025_6299_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4918/11872339/31646f6e42b6/12967_2025_6299_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4918/11872339/ea2abd50b151/12967_2025_6299_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4918/11872339/4f039eb5100c/12967_2025_6299_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4918/11872339/753035024f34/12967_2025_6299_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4918/11872339/0c89026b4fd2/12967_2025_6299_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4918/11872339/9f87e4a4e49b/12967_2025_6299_Fig6_HTML.jpg

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本文引用的文献

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Defining clinically useful biomarkers of immune checkpoint inhibitors in solid tumours.定义实体瘤中免疫检查点抑制剂的临床有用生物标志物。
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TSPAN8 myofibroblastic cancer-associated fibroblasts promote chemoresistance in patients with breast cancer.TSPAN8 肌成纤维细胞性癌症相关成纤维细胞促进乳腺癌患者的化疗耐药性。
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Spatially Segregated Macrophage Populations Predict Distinct Outcomes in Colon Cancer.空间分离的巨噬细胞群体预测结直肠癌的不同结局。
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Single cell deciphering of progression trajectories of the tumor ecosystem in head and neck cancer.单细胞解析头颈部癌症肿瘤生态系统的演进轨迹。
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