泛肿瘤空间转录组学揭示肿瘤组织的保守特性

Pan-tumor spatial transcriptomics reveals conserved properties of tumor organization.

期刊: Cell
PMID: 42664957
原文: PubMed ↗
发布日期: 2026-08-28

作者

Vivek Behera — Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL 60637, USA; Duchossois Family Institute, University of Chicago, Chicago, IL 60637, USA.
Alexander Guzzetta — Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
Hannah Giba — Duchossois Family Institute, University of Chicago, Chicago, IL 60637, USA; Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
Ue-Yu Pen — Duchossois Family Institute, University of Chicago, Chicago, IL 60637, USA; Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
Anna Di Lello — Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL 60637, USA.
Bipul Pandey — Duchossois Family Institute, University of Chicago, Chicago, IL 60637, USA; Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
Benjamin A Doran — Duchossois Family Institute, University of Chicago, Chicago, IL 60637, USA; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, USA.
Alessandra Esposito — Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL 60637, USA.
Apameh Pezeshk — Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL 60637, USA.
Aliya Husain — Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
Christine M Bestvina — Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL 60637, USA.
Justin Kline — Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL 60637, USA.
Marina C Garassino — Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL 60637, USA.
Arjun S Raman — Duchossois Family Institute, University of Chicago, Chicago, IL 60637, USA; Department of Pathology, University of Chicago, Chicago, IL 60637, USA; Center for the Physics of Evolving Systems, University of Chicago, Chicago, IL 60637, USA. Electronic address: araman@bsd.uchicago.edu.

作者单位

Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL 60637, USA; Duchossois Family Institute, University of Chicago, Chicago, IL 60637, USA.
Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
Duchossois Family Institute, University of Chicago, Chicago, IL 60637, USA; Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL 60637, USA.
Duchossois Family Institute, University of Chicago, Chicago, IL 60637, USA; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, USA.
Duchossois Family Institute, University of Chicago, Chicago, IL 60637, USA; Department of Pathology, University of Chicago, Chicago, IL 60637, USA; Center for the Physics of Evolving Systems, University of Chicago, Chicago, IL 60637, USA. Electronic address: araman@bsd.uchicago.edu.

摘要

中文

肿瘤微环境（TME）在组成和功能上具有异质性，使得发现组织结构原理具有挑战性。通过对262例空间转录组学分析的实体瘤研究，我们识别出一种保守结构，其中TME被划分为离散的、分层组织的多细胞亚区，我们称之为“空间组”（SGs）。正如正交空间测量和专家病理学审查所示，SGs与从全局组织背景到局部细胞邻域的可识别生物学域相关联。通过SGs比较肿瘤揭示了一种泛肿瘤分类，其中主要变异轴是免疫生物学的空间异质性。在一项独立的、回顾性的接受免疫检查点阻断（ICB）治疗的非小细胞肺癌患者队列（n=16）中，泛肿瘤空间生物学分类区分了临床反应，并捕获了与ICB敏感性相关的结构和生物学标志。总之，这些发现表明SGs可能是TME的重要组织域，将空间结构、生物学功能和治疗反应联系起来。

English

Tumor microenvironments (TMEs) are compositionally and functionally heterogeneous, making it challenging to discover organizing structural principles. Through a study of 262 solid tumors profiled by spatial transcriptomics, we identify a conserved architecture where TMEs are partitioned into discrete, hierarchically organized multicellular sub-regions, which we term "spatial groups" (SGs). As indicated by orthogonal spatial measurements and expert pathologist review, SGs associate with recognizable biological domains spanning global tissue context to local cellular neighborhoods. Comparing tumors through SGs reveals a pan-tumor classification where the dominant axis of variation is spatial heterogeneity of immune biology. In an independent, retrospective cohort of non-small cell lung cancer patients treated with immune checkpoint blockade (ICB; n = 16), pan-tumor spatial biology classification distinguishes clinical response and captures structural and biological hallmarks associated with ICB sensitivity. Together, these findings suggest that SGs may be important organizing domains of the TME that relate spatial structure, biological function, and response to therapy.

分类与指标

研究类型: 基础研究
病种: 肺癌
JCR 分区: Q1
影响因子: 45.1
新锐分区: 1区