美国国立卫生研究院Xin Wei Wang课题组的最新研究揭示肿瘤细胞的多样性驱动肝癌微环境重编程。2019年10月3日，国际知名学术期刊《癌细胞》在线发表了这一成果。

研究人员确定了来自19位患者肝癌生物标本的单细胞转录组学情况。研究人员发现在肿瘤内部和肿瘤之间的恶性细胞以及肿瘤微环境（TME）的不同情况中，异质性程度不同。令人惊讶的是，转录组多样性较高的肿瘤与患者的整体生存期较差有关。研究人员发现低氧依赖性血管内皮生长因子表达在肿瘤多样性和TME极化之间的联系。此外，来自异质性较高肿瘤的T细胞显示出较低的溶细胞活性。使用765个肝脏肿瘤的整体基因组和转录组谱研究人员发现了一致的结果。这些结果提供了对肝癌多样化生态系统及其对患者预后的影响的见解。

据悉，肿瘤中的细胞多样性是治疗失败和实体恶性肿瘤致死的关键因素。

附：英文原文

Title: Tumor Cell Biodiversity Drives Microenvironmental Reprogramming in Liver Cancer

Author: Lichun Ma, Maria O. Hernandez, Yongmei Zhao, Monika Mehta, Bao Tran, Michael Kelly, Zachary Rae, Jonathan M. Hernandez, Jeremy L. Davis, Sean P. Martin, David E. Kleiner, Stephen M. Hewitt, Kris Ylaya, Bradford J. Wood, Tim F. Greten, Xin Wei Wang

Issue&Volume: 3 October 2019

Abstract: Cellular diversity in tumors is a key factor for therapeutic failures and lethal outcomes of solid malignancies. Here, we determined the single-cell transcriptomic landscape of liver cancer biospecimens from 19 patients. We found varying degrees of heterogeneity in malignant cells within and between tumors and diverse landscapes of tumor microenvironment (TME). Strikingly, tumors with higher transcriptomic diversity were associated with patients worse overall survival. We found a link between hypoxia-dependent vascular endothelial growth factor expression in tumor diversity and TME polarization. Moreover, T cells from higher heterogeneous tumors showed lower cytolytic activities. Consistent results were found using bulk genomic and transcriptomic profiles of 765 liver tumors. Our results offer insight into the diverse ecosystem of liver cancer and its impact on patient prognosis.

DOI: 10.1016/j.ccell.2019.08.007

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(19)30375-7