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新研究绘制出高级浆液性卵巢癌的单细胞图谱
作者:小柯机器人 发布时间:2020/6/28 10:26:00

美国麻省理工学院Aviv Regev研究组绘制出高级浆液性卵巢癌的单细胞图谱。该研究于2020年6月22日在线发表于国际学术期刊《自然—医学》。

为了全面表征晚期高级别浆液性卵巢癌(HGSOC)腹水生态系统,研究人员使用单细胞RNA测序对11例HGSOC患者的22个腹水标本中约11,000个细胞进行了分析。研究人员发现腹水细胞的组成和功能程序(包括免疫调节性成纤维细胞亚群和巨噬细胞群体)的患者间差异很大。研究人员发现以前描述的HGSOC免疫反应性和间充质亚型具有预后意义,这反映了免疫浸润和成纤维细胞的丰富性,而不是恶性细胞的不同亚群。恶性细胞变异性的部分原因是异质拷贝数改变模式或干性程序的表达。

恶性细胞共享炎症程序的表达,这些炎症程序在从另外收集的样本中的约35,000个细胞的单细胞RNA测序中得到了重现,其中包括三个腹水、两个原发HGSOC肿瘤和三个患者腹水衍生的异种移植模型。在恶性细胞和与癌症相关成纤维细胞中JAK/STAT途径的抑制在短期培养和患者来源的异种移植模型中具有有效的抗肿瘤活性。这些工作有助于解析HSGOC,并为开发新型治疗方法提供了资源。

据悉,晚期高级别浆液性卵巢癌(HGSOC)的女性经常发生恶性腹水,并与耐药性和预后不良相关。

附:英文原文

Title: A single-cell landscape of high-grade serous ovarian cancer

Author: Benjamin Izar, Itay Tirosh, Elizabeth H. Stover, Isaac Wakiro, Michael S. Cuoco, Idan Alter, Christopher Rodman, Rachel Leeson, Mei-Ju Su, Parin Shah, Marcin Iwanicki, Sarah R. Walker, Abhay Kanodia, Johannes C. Melms, Shaolin Mei, Jia-Ren Lin, Caroline B. M. Porter, Michal Slyper, Julia Waldman, Livnat Jerby-Arnon, Orr Ashenberg, Titus J. Brinker, Caitlin Mills, Meri Rogava, Sbastien Vigneau, Peter K. Sorger, Levi A. Garraway, Panagiotis A. Konstantinopoulos, Joyce F. Liu, Ursula Matulonis, Bruce E. Johnson, Orit Rozenblatt-Rosen, Asaf Rotem, Aviv Regev

Issue&Volume: 2020-06-22

Abstract: Malignant abdominal fluid (ascites) frequently develops in women with advanced high-grade serous ovarian cancer (HGSOC) and is associated with drug resistance and a poor prognosis1. To comprehensively characterize the HGSOC ascites ecosystem, we used single-cell RNA sequencing to profile ~11,000 cells from 22 ascites specimens from 11 patients with HGSOC. We found significant inter-patient variability in the composition and functional programs of ascites cells, including immunomodulatory fibroblast sub-populations and dichotomous macrophage populations. We found that the previously described immunoreactive and mesenchymal subtypes of HGSOC, which have prognostic implications, reflect the abundance of immune infiltrates and fibroblasts rather than distinct subsets of malignant cells2. Malignant cell variability was partly explained by heterogeneous copy number alteration patterns or expression of a stemness program. Malignant cells shared expression of inflammatory programs that were largely recapitulated in single-cell RNA sequencing of ~35,000 cells from additionally collected samples, including three ascites, two primary HGSOC tumors and three patient ascites-derived xenograft models. Inhibition of the JAK/STAT pathway, which was expressed in both malignant cells and cancer-associated fibroblasts, had potent anti-tumor activity in primary short-term cultures and patient-derived xenograft models. Our work contributes to resolving the HSGOC landscape3,4,5 and provides a resource for the development of novel therapeutic approaches.

DOI: 10.1038/s41591-020-0926-0

Source: https://www.nature.com/articles/s41591-020-0926-0

期刊信息

Nature Medicine:《自然—医学》,创刊于1995年。隶属于施普林格·自然出版集团,最新IF:30.641
官方网址:https://www.nature.com/nm/
投稿链接:https://mts-nmed.nature.com/cgi-bin/main.plex