新研究繪製出高級漿液性卵巢癌的單細胞圖譜
作者：
小柯機器人發布時間：2020/6/28 10:26:00
美國麻省理工學院Aviv Regev研究組繪製出高級漿液性卵巢癌的單細胞圖譜。該研究於2020年6月22日在線發表於國際學術期刊《自然—醫學》。
為了全面表徵晚期高級別漿液性卵巢癌（HGSOC）腹水生態系統，研究人員使用單細胞RNA測序對11例HGSOC患者的22個腹水標本中約11,000個細胞進行了分析。研究人員發現腹水細胞的組成和功能程序（包括免疫調節性成纖維細胞亞群和巨噬細胞群體）的患者間差異很大。研究人員發現以前描述的HGSOC免疫反應性和間充質亞型具有預後意義，這反映了免疫浸潤和成纖維細胞的豐富性，而不是惡性細胞的不同亞群。惡性細胞變異性的部分原因是異質拷貝數改變模式或乾性程序的表達。
惡性細胞共享炎症程序的表達，這些炎症程序在從另外收集的樣本中的約35,000個細胞的單細胞RNA測序中得到了重現，其中包括三個腹水、兩個原發HGSOC腫瘤和三個患者腹水衍生的異種移植模型。在惡性細胞和與癌症相關成纖維細胞中JAK/STAT途徑的抑制在短期培養和患者來源的異種移植模型中具有有效的抗腫瘤活性。這些工作有助於解析HSGOC，並為開發新型治療方法提供了資源。
據悉，晚期高級別漿液性卵巢癌（HGSOC）的女性經常發生惡性腹水，並與耐藥性和預後不良相關。
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