首页|Immune-tumor interaction dictates spatially directed evolution of esophageal squamous cell carcinoma

Immune-tumor interaction dictates spatially directed evolution of esophageal squamous cell carcinoma

扫码查看
原文链接
  • NETL
  • NSTL
  • 万方数据
Esophageal squamous cell carcinoma(ESCC)is a poor-prognostic cancer type with extensive intra-and inter-patient heterogeneity in both genomic variations and tumor microenvironment(TME).However,the patterns and drivers of spatial genomic and microenvironmental heterogeneity of ESCC remain largely unknown.Here,we generated a spatial multi-omic atlas by whole-exome,transcriptome,and methylome sequencing of507 tumor samples from 103 patients.We identified a novel tumor suppressor PREX2,accounting for 22％of ESCCs with frequent somatic mutations or hyper-methylation,which promoted migration and invasion of ESCC cells in vitro.Analysis of the TME and quantification of subclonal expansion indicated that ESCCs undergo spatially directed evolution,where subclones mostly originated from the tumor center but had a biased clonal expansion to the upper direction of the esophagus.Interestingly,we found upper regions of ESCCs often underwent stronger immunoediting with increased selective fitness,suggesting more stringent immune selection.In addition,distinct TMEs were associated with variable genomic and clinical outcomes.Among them,hot TME was associated with high immune evasion and subclonal heterogeneity.We also found that immunoediting,instead of CD8+T cell abundance,acts as an independent prognostic factor of ESCCs.Importantly,we found significant heterogeneity in previously considered potential therapeutic targets,as well as BRCAness characteristics in a subset of patients,emphasizing the importance of focusing on heterogeneity in ESCC targeted therapy.Collectively,these findings provide novel insights into the mechanisms of the spatial evolution of ESCC and inform precision therapeutic strategies.

squamous cell carcinomaheterogeneitymulti-omicsevolutiontumor microenvironment

Yong Zhou、Shanlan Mo、Heyang Cui、Ruifang Sun、Weimin Zhang、Xiaofei Zhuang、Enwei Xu、Hongyi Li、Yikun Cheng、Yongsheng Meng、Meilin Liu、Ting Yan、Huijuan Liu、Ling Zhang、Bin Yang、Yanfeng Xi、Shubin Wang、Xiaolong Cheng、ShuaiCheng Li、Zhihua Liu、Qimin Zhan、Zheng Hu、Yongping Cui

展开 >

Cancer Institute,Department of Pathology,Peking University Shenzhen Hospital,Shenzhen Peking University-the Hong Kong University of Science and Technology(PKU-HKUST)Medical Center

Institute of Cancer Research,Shenzhen Bay Laboratory,Shenzhen 518000,China

Key Laboratory of Cellular Physiology of the Ministry of Education,Department of Pathology,Shanxi Medical University,Taiyuan 030001,China

City University of Hong Kong Shenzhen Research Institute,Shenzhen 518000,China

CAS Key Laboratory of Quantitative Engineering Biology,Shenzhen Institute of Synthetic Biology,Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen 518000,China

Department of Surgery,Faculty of Medicine,The Chinese University of Hong Kong,Hong Kong 999077,China

Department of Tumor Biobank,Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital,Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University,Taiyuan 030013,China

Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing),Laboratory of Molecular Oncology,Peking University Cancer Hospital & Institute,Beijing 100142,China

Research Unit of Molecular Cancer Research,Chinese Academy of Medi

Department of Thoracic Surgery,Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital,Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University,Taiyuan 030013,China

Department of Pathology,Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital,Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University,Taiyuan 030013,China

College of Letters &Science,University of California Berkeley,Berkeley,CA 94704,USA

State Key Laboratory of Molecular Oncology,National Cancer Center/Natlonal Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China

展开 >

Guangdong Basic and Applied Basic Research FoundationShenzhen Medical Research Funds国家重点研发计划Major Program of Shenzhen Bay LaboratoryShenzhen Bay Laboratory Open Program国家自然科学基金国家自然科学基金国家自然科学基金国家自然科学基金国家自然科学基金国家自然科学基金国家自然科学基金国家自然科学基金Shenzhen Project of Science and TechnologyCAMS Innovation Fund for Medical SciencesFund for Shanxi'1331 Project'to YPC and the special fund for Science and Technology Innovation Teams of Shanxi ProvinceFund for Shanxi'1331 Project'to YPC and the special fund for Science and Technology Innovation Teams of Shanxi ProvinceGuangdong Basic and Applied Basic Research FoundationShenzhen Science and Technology Innovation Commission ProjectShenzhen Science and Technology Innovation Commission ProjectShenzhen Science and Technology Innovation Commission ProjectShenzhen Science and Technology Innovation Commission Project

2019B030302012C23030022021YFC2501001S201101004SZBL20200905010038234102432270693U21A203728197261381988101821729308230291682241236JCYJ201908130942036002019-I2M-5-081201605D131045-162022040510010242021B1515020042ZDSYS20190902092855097KCXFZ20200201101050887GJHZ20200731095207023RCBS20210609104515040

2024

10.1093/nsr/nwae150

国家科学评论(英文版)

国家科学评论(英文版)

CSTPCD
ISSN：
年,卷(期)：2024.11(5)
  • 39