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原发性和转移性脑肿瘤的单细胞空间免疫图谱。

Single-cell spatial immune landscapes of primary and metastatic brain tumours.

机构信息

Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.

Department of Physiology, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.

出版信息

Nature. 2023 Feb;614(7948):555-563. doi: 10.1038/s41586-022-05680-3. Epub 2023 Feb 1.

DOI:10.1038/s41586-022-05680-3
PMID:36725935
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9931580/
Abstract

Single-cell technologies have enabled the characterization of the tumour microenvironment at unprecedented depth and have revealed vast cellular diversity among tumour cells and their niche. Anti-tumour immunity relies on cell-cell relationships within the tumour microenvironment, yet many single-cell studies lack spatial context and rely on dissociated tissues. Here we applied imaging mass cytometry to characterize the immunological landscape of 139 high-grade glioma and 46 brain metastasis tumours from patients. Single-cell analysis of more than 1.1 million cells across 389 high-dimensional histopathology images enabled the spatial resolution of immune lineages and activation states, revealing differences in immune landscapes between primary tumours and brain metastases from diverse solid cancers. These analyses revealed cellular neighbourhoods associated with survival in patients with glioblastoma, which we leveraged to identify a unique population of myeloperoxidase (MPO)-positive macrophages associated with long-term survival. Our findings provide insight into the biology of primary and metastatic brain tumours, reinforcing the value of integrating spatial resolution to single-cell datasets to dissect the microenvironmental contexture of cancer.

摘要

单细胞技术使人们能够以前所未有的深度描述肿瘤微环境，并揭示肿瘤细胞及其龛位之间巨大的细胞多样性。抗肿瘤免疫依赖于肿瘤微环境中的细胞间关系，但许多单细胞研究缺乏空间背景且依赖于分离的组织。在这里，我们应用成像质谱细胞术来描述 139 例高级别神经胶质瘤和 46 例脑转移瘤患者的免疫图谱。对超过 110 万个细胞进行单细胞分析，涉及 389 个高维组织病理学图像，从而能够对免疫谱系和激活状态进行空间解析，揭示了原发肿瘤和来自不同实体瘤的脑转移瘤之间免疫图谱的差异。这些分析揭示了与胶质母细胞瘤患者生存相关的细胞邻域，我们利用这些信息鉴定了与长期生存相关的髓过氧化物酶 (MPO)阳性巨噬细胞的独特群体。我们的研究结果深入了解了原发性和转移性脑肿瘤的生物学，强化了将空间分辨率与单细胞数据集整合以剖析癌症微环境结构的价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfe5/9931580/daef371a19e2/41586_2022_5680_Fig14_ESM.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfe5/9931580/092db17a3c56/41586_2022_5680_Fig9_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfe5/9931580/75ddf5a3f056/41586_2022_5680_Fig10_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfe5/9931580/16d58634d843/41586_2022_5680_Fig11_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfe5/9931580/207c8d73b396/41586_2022_5680_Fig12_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfe5/9931580/c5fdba00a728/41586_2022_5680_Fig13_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfe5/9931580/daef371a19e2/41586_2022_5680_Fig14_ESM.jpg

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本文引用的文献

[1]
T-cell dysfunction in the glioblastoma microenvironment is mediated by myeloid cells releasing interleukin-10.

Nat Commun. 2022-2-17

[2]
Imaging mass cytometry and multiplatform genomics define the phenogenomic landscape of breast cancer.

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