小柯机器人

英国韦尔科姆基金会桑格研究所Thomas J. Mitchell等研究人员合作绘制出肾癌瘤内和相关区域的单细胞转录组图谱。这一研究成果于2022年11月23日在线发表在国际学术期刊《癌细胞》上。

研究人员表示，肿瘤行为错综复杂地依赖于癌细胞的致癌特性及其多细胞的相互作用。

为了了解更广泛的微环境中的这些依赖性，研究人员报道了12名肾脏肿瘤患者的27万多个单细胞转录组和100个显微切割组织的全外显子，然后用空间转录组学进行验证。这些组织取自肿瘤核心、肿瘤-正常界面、周围正常组织和外周血等多个区域。研究人员发现，CD8⁺T细胞克隆型的组织类型位置在很大程度上定义了它们的耗竭状态，而肿瘤内的空间异质性并不能很好地解释体细胞异质性。来自单细胞RNA测序数据的新突变调用使研究人员能够广泛地推断基质细胞的克隆性和谱系追踪髓系细胞的发展。

研究人员报告了区分肿瘤细胞功能的六个保守元程序，并发现一个上皮-间质转化元程序在肿瘤-正常界面高度富集，与表达IL1B的巨噬细胞共同定位，这提供一个潜在的治疗靶标。

附：英文原文

Title: Mapping single-cell transcriptomes in the intra-tumoral and associated territories of kidney cancer

Author: Ruoyan Li, John R. Ferdinand, Kevin W. Loudon, Georgina S. Bowyer, Sean Laidlaw, Francesc Muyas, Lira Mamanova, Joana B. Neves, Liam Bolt, Eirini S. Fasouli, Andrew R.J. Lawson, Matthew D. Young, Yvette Hooks, Thomas R.W. Oliver, Timothy M. Butler, James N. Armitage, Tev Aho, Antony C.P. Riddick, Vincent Gnanapragasam, Sarah J. Welsh, Kerstin B. Meyer, Anne Y. Warren, Maxine G.B. Tran, Grant D. Stewart, Isidro Cortés-Ciriano, Sam Behjati, Menna R. Clatworthy, Peter J. Campbell, Sarah A. Teichmann, Thomas J. Mitchell

Issue&Volume: 2022-11-23

Abstract: Tumor behavior is intricately dependent on the oncogenic properties of cancer cells and their multi-cellular interactions. To understand these dependencies within the wider microenvironment, we studied over 270,000 single-cell transcriptomes and 100 microdissected whole exomes from 12 patients with kidney tumors, prior to validation using spatial transcriptomics. Tissues were sampled from multiple regions of the tumor core, the tumor-normal interface, normal surrounding tissues, and peripheral blood. We find that the tissue-type location of CD8+ T cell clonotypes largely defines their exhaustion state with intra-tumoral spatial heterogeneity that is not well explained by somatic heterogeneity. De novo mutation calling from single-cell RNA-sequencing data allows us to broadly infer the clonality of stromal cells and lineage-trace myeloid cell development. We report six conserved meta-programs that distinguish tumor cell function, and find an epithelial-mesenchymal transition meta-program highly enriched at the tumor-normal interface that co-localizes with IL1B-expressing macrophages, offering a potential therapeutic target.

DOI: 10.1016/j.ccell.2022.11.001

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(22)00548-7

Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
官方网址：https://www.cell.com/cancer-cell/home
投稿链接：https://www.editorialmanager.com/cancer-cell/default.aspx