小柯机器人

科学家绘制出肺腺癌中免疫细胞的空间位置图谱
2020-05-28 18:25

英国癌症研究所Yinyin Yuan、伦敦大学学院Charles Swanton、剑桥大学John Le Quesne等研究人员合作绘制了肺腺癌中免疫细胞的空间位置图谱。这一研究成果于2020年5月27日在线发表在《自然—医学》上。

研究人员将多区域外显子组和RNA测序(RNA-seq)数据与空间组织学信息进行了整合。这些空间组织学信息通过深度学习在TRACERx队列中的100例非小细胞肺癌患者中产生。来自免疫冷区的癌症亚克隆在突变空间中的相关性更高,比来自免疫热区的亚克隆更多样化。在TRACERx和970例肺腺癌的独立多样本队列中,超过一个免疫冷区的肿瘤复发风险更高,与肿瘤大小、分期和样本数无关。
 
在肺腺癌中(而不是肺鳞状细胞癌),在不破坏抗原呈递的情况下,肿瘤区域中癌-基质细胞界面的几何不规则性和复杂性显著增加。在具有低克隆新抗原负担的肿瘤中观察到相邻基质中淋巴细胞积累的减少。总的来说,免疫空间位置变异性阐明了肿瘤生态学中的限制因素,这些因素可能会影响免疫逃避的亚克隆和侵袭性临床表型的出现。
 
据了解,分子分析方面的显著进展提高人们对癌细胞免疫逃逸进化的理解。然而,尚未阐明免疫和基质细胞的空间构象,这可能揭示免疫逃逸在肿瘤空间位置的进化。
 
附:英文原文

Title: Geospatial immune variability illuminates differential evolution of lung adenocarcinoma

Author: Khalid AbdulJabbar, Shan E. Ahmed Raza, Rachel Rosenthal, Mariam Jamal-Hanjani, Selvaraju Veeriah, Ayse Akarca, Tom Lund, David A. Moore, Roberto Salgado, Maise Al Bakir, Luis Zapata, Crispin T. Hiley, Leah Officer, Marco Sereno, Claire Rachel Smith, Sherene Loi, Allan Hackshaw, Teresa Marafioti, Sergio A. Quezada, Nicholas McGranahan, John Le Quesne, Charles Swanton, Yinyin Yuan

Issue&Volume: 2020-05-27

Abstract: Remarkable progress in molecular analyses has improved our understanding of the evolution of cancer cells toward immune escape1,2,3,4,5. However, the spatial configurations of immune and stromal cells, which may shed light on the evolution of immune escape across tumor geographical locations, remain unaddressed. We integrated multiregion exome and RNA-sequencing (RNA-seq) data with spatial histology mapped by deep learning in 100 patients with non-small cell lung cancer from the TRACERx cohort6. Cancer subclones derived from immune cold regions were more closely related in mutation space, diversifying more recently than subclones from immune hot regions. In TRACERx and in an independent multisample cohort of 970 patients with lung adenocarcinoma, tumors with more than one immune cold region had a higher risk of relapse, independently of tumor size, stage and number of samples per patient. In lung adenocarcinoma, but not lung squamous cell carcinoma, geometrical irregularity and complexity of the cancer–stromal cell interface significantly increased in tumor regions without disruption of antigen presentation. Decreased lymphocyte accumulation in adjacent stroma was observed in tumors with low clonal neoantigen burden. Collectively, immune geospatial variability elucidates tumor ecological constraints that may shape the emergence of immune-evading subclones and aggressive clinical phenotypes.

DOI: 10.1038/s41591-020-0900-x

Source: https://www.nature.com/articles/s41591-020-0900-x

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:87.241
官方网址:https://www.nature.com/nm/
投稿链接:https://mts-nmed.nature.com/cgi-bin/main.plex


本期文章:《自然—医学》:Online/在线发表

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