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Transition from pre-invasive to invasive adenocarcinoma reveals increased Treg cells, exhausted CD8+ T cells, reduced cytotoxicity, and invasive tumors with higher neoantigen load and a more diverse TCR repertoire.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/genomic-and-immune-heterogeneity-of-multiple-synchronous-lung-adenocarcinoma-at-different-developmental-stages/331273/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/genomic-and-immune-heterogeneity-of-multiple-synchronous-lung-adenocarcinoma-at-different-developmental-stages/331273.png","ImageObject",300,407,{"name":42,"@type":43},"Theodore","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-23","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",6,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What data types were used to study MSLCs in this research?","Question",{"text":63,"@type":64},"The study integrates single-cell RNA-seq, single-cell TCR sequencing, and bulk whole-exome sequencing on 16 MSLCs from 8 patients, with matched normal lung tissues for mutation identification.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How do tumor origins in MSLC patients differ according to the study?",{"text":68,"@type":64},"The tumors are clonally independent with convergent evolution driven by shared driver mutations, and tumors from the same individual show few shared mutations, indicating independent origins.",{"name":70,"@type":61,"acceptedAnswer":71},"What immune and neoantigen changes occur when adenocarcinoma progresses from pre-invasive to invasive stages?",{"text":72,"@type":64},"Progression is associated with more Treg cells and more exhausted CD8+ T cells, along with diminished cytotoxicity. Invasive adenocarcinomas also show greater neoantigen abundance and a more diverse TCR repertoire.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},331273,1790174019,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,105,110,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},"Technology",50,"technology",{"id":106,"doc_module":4,"doc_module_name":25,"category_name":107,"show_sort_weight":108,"slug":109},7,"Healthcare",40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":112,"slug":113},8,30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":111,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145,"preview_page_count":4},7971461740886,"https://ap-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","Article [https://doi.org/10.1038/s41467-024-52139-2](https://doi.org/10.1038/s41467-024-52139-2)  \nGenomic and immune heterogeneity of multiple synchronous lung adenocarcinoma at different developmental stages  \nReceived: 12 September 2023  \n\n| Accepted: 28 August 2024 |\n| --- |\n| |\n| Check for updates |\n\nYue Zhao 1,2,3,11 , Jian Gao 1,2,3,4,11, Jun Wang 5,11, Fanfan Fan1,2,3,11,  \nChao Cheng6,11, Danwen Qian 7,8,11, Ran Guo1,2,3, Yang Zhang1,2,3, Ting Ye1,2,3, Marcellus Augustine7,8,9, Yicong Lin3,10, Jun Shang 1,2,3, Hang Li1,2,3,  \nYunjian Pan1,2,3, Qingyuan Huang1,2,3, Haiqing Chen1,2,3, Han Han1,2,3, Zhendong Gao1,2,3, Qiming Wang5, Shiyue Zhang5, Mou Zhang5, Fangqiu Fu1,2,3, Yueren Yan1,2,3, Shanila Fernandez Patel7,8, Roberto Vendramin 7,8, Hui Yuan1,2,3, Yawei Zhang1,2,3, Jiaqing Xiang1,2,3, Hong Hu1,2,3, Yihua Sun 1,2,3, Yuan Li 3,10, Kevin Litchfield7,8 , Zhiwei Cao 4,5  & Haiquan Chen 1,2,3   \nMultiple synchronous lung cancers (MSLCs) constitute a unique subtype of lung cancer. To explore the genomic and immune heterogeneity across different pathological stages of MSLCs, we analyse 16 MSLCs from 8 patients using single-cell RNA-seq, single-cell TCR sequencing, and bulk whole-exome sequencing. Our investigation indicates clonally independent tumours with convergent evolution driven by shared driver mutations. However, tumours from the same individual exhibit few shared mutations, indicating independent origins. During the transition from pre-invasive to invasive adenocarcinoma, we observe a shift in T cell phenotypes characterized by increased Treg cells and exhausted CD8+ T cells, accompanied by diminished cytotoxicity. Additionally, invasive adenocarcinomas exhibit greater neoantigen abundance and a more diverse TCR repertoire, indicating heightened heterogeneity. In summary, despite having a common genetic background and environmental exposure, our study emphasizes the individuality of MSLCs at different stages, highlighting their unique genomic and immune characteristics.  \nLung cancer is one of the deadliest diseases worldwide, with lung adenocarcinoma (LUAD) being the most common histological subtype1,2. Advances in next-generation sequencing techniques have revolutionised the field of molecular profiling, enabling personalised treatment  \nstrategies based on specific driver mutations present in patients3–7. Additionally, immune checkpoint inhibitors (ICIs) have shown promising results in improving the survival of lung cancer patients, although reliable biomarkers for predicting treatment response to ICIs have not  \n1Departments of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai, China. 2Institute of Thoracic Oncology, Fudan University, Shanghai, China. 3Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. 4International Human Phenome Institutes (Shanghai), Shanghai, China. 5School of Life Sciences, Fudan University, Shanghai, China. 6Department of Thoracic Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China. 7Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK. 8Tumour Immunogenomics and Immunosurveillance Laboratory, University College London Cancer Institute, London, UK. 9Division of Medicine, University College London, London, UK. 10Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China. 11These authors contributed equally: Yue Zhao, Jian Gao, Jun Wang, Fanfan Fan, Chao Cheng, Danwen Qian. e-mail: [yuezhao97@outlook.com](yuezhao97@outlook.com);  \nk. litchfi[eld@ucl.ac.uk](eld@ucl.ac.uk); [zwcao@fudan.edu.cn](zwcao@fudan.edu.cn); [hqchen1@yahoo.com](hqchen1@yahoo.com)  \nbeen fully discovered8–12. Therefore, a comprehensive understanding of the molecular profile and immune microenvironment ofLUADis crucial.  \nMultiple synchronous lung cancers (MSLCs) represent a unique subtype of lung cancer, characterised by th","cbCaibp9OvCryCZ1","https://ap.wps.com/l/cbCaibp9OvCryCZ1","pdf",2517069,14,"English","# Results\n## Somatic mutation landscape demonstrates inter-tumour heterogeneity and different evolutionary patterns of multiple synchronous lung cancers (MSLCs)","[{\"question\":\"What data types were used to study MSLCs in this research?\",\"answer\":\"The study integrates single-cell RNA-seq, single-cell TCR sequencing, and bulk whole-exome sequencing on 16 MSLCs from 8 patients, with matched normal lung tissues for mutation identification.\"},{\"question\":\"How do tumor origins in MSLC patients differ according to the study?\",\"answer\":\"The tumors are clonally independent with convergent evolution driven by shared driver mutations, and tumors from the same individual show few shared mutations, indicating independent origins.\"},{\"question\":\"What immune and neoantigen changes occur when adenocarcinoma progresses from pre-invasive to invasive stages?\",\"answer\":\"Progression is associated with more Treg cells and more exhausted CD8+ T cells, along with diminished cytotoxicity. Invasive adenocarcinomas also show greater neoantigen abundance and a more diverse TCR repertoire.\"}]","Genomic and immune heterogeneity of multiple synchronous lung adenocarcinoma at different developmental stages | PDF",1789992512,35]