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PLCs develop within a dynamic tumor ecosystem composed of malignant, immune, and stromal cells. Single-cell and spatial multi-omics sequencing enables analysis of spatiotemporal interactions among heterogeneous cell populations to clarify mechanisms of tumorigenesis, recurrence, and treatment resistance and support identification of novel therapeutic targets.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/dissecting-the-tumor-ecosystem-of-liver-cancers-in-the-single-cell-era/379174/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/dissecting-the-tumor-ecosystem-of-liver-cancers-in-the-single-cell-era/379174.png","ImageObject",300,407,{"name":92,"@type":93},"Melati","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the main focus of the review on liver cancers?","Question",{"text":112,"@type":113},"The review focuses on dissecting the tumor ecosystem of primary liver cancers to understand mechanisms underlying tumorigenesis, relapse, and treatment resistance.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Why are primary liver cancers associated with poor prognosis?",{"text":117,"@type":113},"They are often linked to high relapse rates and low therapeutic response rates, which together contribute to worse outcomes.",{"name":119,"@type":110,"acceptedAnswer":120},"How do single-cell and spatial multi-omics methods help?",{"text":121,"@type":113},"They provide an opportunity to elucidate spatiotemporal interactions among heterogeneous cell types within the complex tumor ecosystem, supporting deeper mechanistic insight.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},379174,1790246942,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":29,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":41},962085570644,"https://ap-avatar.wpscdn.com/davatar_994ba38a5ba835b3df7d355c54d3ed8d","DOI: 10.1097/HC9.0000000000000248  \nINVIT E D: REVIEW  \nDissecting the tumor ecosystem of liver cancers in the single-cell era  \nYue Wang  | Pengxiang Wang  | Zefan Zhang  | Jian Zhou  | Jia Fan  | Yunfan Sun   \nDepartment of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China  \nCorrespondence  \nYunfan Sun, Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, China.  \nEmail: [yunfan_sun@msn.com](yunfan_sun@msn.com)  \n\n|  | Abstract |  |\n| --- | --- | --- |\n| | Primary liver cancers (PLCs) are a broad class of malignancies that include HCC, intrahepatic cholangiocarcinoma, and combined hepatocellular and intrahepatic cholangiocarcinoma. PLCs are often associated with a poor prognosis due to their high relapse and low therapeutic response rates. Importantly, PLCs exist within a dynamic and complex tumor ecosystem, which includes malignant, immune, and stromal cells. It is critical to dissect the PLC tumor ecosystem to uncover the underlying mechanisms associated with tumorigenesis, relapse, and treatment resistance to facilitate the discovery of novel therapeutic targets. Single-cell and spatial multi-omics sequencing techniques offer an unprecedented opportunity to elucidatespatiotemporal interactions among heterogeneous cell types within the complex tumor ecosystem. In this review, we describe the latest advances in single-cell and spatial technologies and review their applications with respect to dissecting liver cancer tumor ecosystems. |  |\n|  |  |  |\n\nINTRODUCTION  \nIn a natural ecosystem, the phenomenon known as“survival of the fittest” postulates that organisms best adapted to their environment can cope with external selection pressures, thereby surviving and evolving over time. [1,2] From an ecological viewpoint, the process of tumor initiation and progression is analogous to the introduction of an invasive biological species in nature. After the transformation of normal  \ncells to abnormal tumor cells (invasive species), they constantly adapt and remodel the environment they inhabit to support their proliferation and metastasis, which eventually disrupts normal biological function in the affected organ and organism (habitat) . [3–6] The current understanding of cancer is that it is not only a genetic disease of malignant cells but also a disease that affects the complex tumor ecosystem. The tumor ecosystem is composed of tumor cells, the local tumor microenvironment (TME), distant organ niches, and  \nAbbreviations: CAFs, cancer-associated fibroblasts; CTCs, circulating tumor cells; DCs, dendritic cells; DPT, double-positive T; HLA LOH, Human leukocyte Ag loss of heterozygosity; ICB, immune checkpoint blockade; iCCA, intrahepatic cholangiocarcinoma; ICIs, Immune checkpoint inhibitors; NK cells, natural killer cells; PLCs, primary liver cancers; TAMs, tumor-associated macrophages; TILs, Tumor-infiltrating lymphocytes; TLSs, Tertiary lymphatic structures; TIME, tumor immune microenvironment; TME, tumor microenvironment.  \n-- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- ----- -  \nThis is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.  \nCopyright © 2023 The Author(s) . Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.  \nimmune, nervous, and endocrine systems. The concept of the cancer ecosystem extended our traditional understanding of tumor biology beyond its local interplay w","cbCailwA3xZthHqI","https://ap.wps.com/l/cbCailwA3xZthHqI","pdf",542512,12,"English","# Introduction\n## Tumor ecosystem concept\n## Primary liver cancer background","[{\"question\":\"What is the main focus of the review on liver cancers?\",\"answer\":\"The review focuses on dissecting the tumor ecosystem of primary liver cancers to understand mechanisms underlying tumorigenesis, relapse, and treatment resistance.\"},{\"question\":\"Why are primary liver cancers associated with poor prognosis?\",\"answer\":\"They are often linked to high relapse rates and low therapeutic response rates, which together contribute to worse outcomes.\"},{\"question\":\"How do single-cell and spatial multi-omics methods help?\",\"answer\":\"They provide an opportunity to elucidate spatiotemporal interactions among heterogeneous cell types within the complex tumor ecosystem, supporting deeper mechanistic insight.\"}]","Dissecting the tumor ecosystem of liver cancers in the single-cell era | PDF",1790234427]