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通过单细胞转录组学描绘转移性卵巢癌的肿瘤微环境。

Characterizing the tumor microenvironment of metastatic ovarian cancer by single-cell transcriptomics.

机构信息

Section of Genetic Medicine, Department of Medicine, University of Chicago, 5841 S. Maryland Avenue, Chicago, IL 60637, USA.

Section of Genetic Medicine, Department of Medicine, University of Chicago, 5841 S. Maryland Avenue, Chicago, IL 60637, USA.

出版信息

Cell Rep. 2021 May 25;35(8):109165. doi: 10.1016/j.celrep.2021.109165.

DOI:10.1016/j.celrep.2021.109165
PMID:34038734
Abstract

Understanding the cellular composition of the tumor microenvironment and the interactions of the cells is essential to the development of successful immunotherapies in cancer. We perform single-cell RNA sequencing (scRNA-seq) of 9,885 cells isolated from the omentum in 6 patients with ovarian cancer and identify 9 major cell types, including cancer, stromal, and immune cells. Transcriptional analysis of immune cells stratifies our patient samples into 2 groups: (1) high T cell infiltration (high T) and (2) low T cell infiltration (low T). TOX-expressing resident memory CD8 T (CD8 Trm) and granulysin-expressing CD4 T cell clusters are enriched in the high T group. Concurrently, we find unique plasmablast and plasma B cell clusters, and finally, NR1H2IRF8 and CD274 macrophage clusters, suggesting an anti-tumor response in the high T group. Our scRNA-seq study of metastatic tumor samples provides important insights in elucidating the immune response within ovarian tumors.

摘要

了解肿瘤微环境的细胞组成和细胞间的相互作用对于癌症免疫疗法的成功发展至关重要。我们对 6 名卵巢癌患者的大网膜中分离出的 9885 个细胞进行了单细胞 RNA 测序 (scRNA-seq),并鉴定出 9 种主要细胞类型,包括癌症细胞、基质细胞和免疫细胞。对免疫细胞的转录分析将我们的患者样本分为 2 组:(1)高 T 细胞浸润 (高 T) 和 (2)低 T 细胞浸润 (低 T)。表达 TOX 的驻留记忆 CD8 T (CD8 Trm) 和表达颗粒酶的 CD4 T 细胞簇在高 T 组中富集。同时,我们发现了独特的浆母细胞和浆细胞簇,以及最后,NR1H2IRF8 和 CD274 巨噬细胞簇,提示高 T 组存在抗肿瘤反应。我们对转移性肿瘤样本的 scRNA-seq 研究为阐明卵巢肿瘤内的免疫反应提供了重要的见解。

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