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Background context links limited ICB efficacy to inadequate cytotoxic lymphocyte trafficking into tumours. Paired adjacent and cancer tissues undergo RNA-seq, with BMP9 identified using Cytoscape and validation via specimens and GEO datasets. Mechanistic and functional assays evaluate BMP9 effects in cells and animals, using ultrasound-targeted microbubble destruction delivery with NK-cell activity and PD-L1 antibody combination in xenografts.",{"@graph":69,"@context":123},[70,84,106],{"@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/bmp9-induced-vascular-normalisation-improves-the-efficacy-of-immunotherapy-against-hepatitis-b-virus-associated-hepatocellular-carcinoma/376741/",{"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/bmp9-induced-vascular-normalisation-improves-the-efficacy-of-immunotherapy-against-hepatitis-b-virus-associated-hepatocellular-carcinoma/376741.png","ImageObject",300,407,{"name":92,"@type":93},"Oliver","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-02","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",13,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What problem does the study address in hepatitis B virus-associated HCC immunotherapy?","Question",{"text":113,"@type":114},"The study addresses limited effectiveness of immune checkpoint blocking by focusing on the reduced trafficking of cytotoxic lymphocytes into tumours, which is critical for successful ICB.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How was BMP9 related to vascular normalisation identified and validated?",{"text":118,"@type":114},"BMP9 was identified via RNA-seq analysis using Cytoscape, and then validated using clinical specimens and Gene Expression Omnibus (GEO) datasets for HCC.",{"name":120,"@type":111,"acceptedAnswer":121},"What delivery approach and therapeutic combination were tested?",{"text":122,"@type":114},"An ultrasound-targeted microbubble destruction (UTMD)-mediated BMP9 delivery strategy was used to normalise tumour vasculature, and therapeutic efficacy was evaluated with cytotoxic lymphocytes (NK cells) combined with a PD-L1 antibody in human cancer xenografts.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},376741,1790794725,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},8796095461610,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","DOI: 10.1002/ctm2.1247  \nRESEARCH ARTICLE  \nBMP9-induced vascular normalisation improves the efficacy of immunotherapy against hepatitis B virus-associated hepatocellular carcinoma  \nYulong Han1 ,\\#  Qiuzhong Pan1 ,\\#  Zhixing Guo1,2 ,\\#  Yufei Du1  Yaojun Zhang3  Yingying Liu4  Jingjing Zhao1  Jinfeng Xu4  Jieying Yang1  Dijun Ouyang1  Yan Tang1  Qijing Wang1  Yongqiang Li1  Jia He1  Mengjuan Yang1  Hao Chen1  Chaopin Yang1  Xinyi Yang1  Jinqi You1  Yuanyuan Chen1  Minghao Ren5  Yao Zhu4, 6  Jianchuan Xia1   Tong Xiang1   \n1 Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P. R. China  \n2 Department of Ultrasound, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P. R. China  \n3 Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P. R. China  \n4 Department of Ultrasonography, Shenzhen Medical Ultrasound Engineering Center, Shenzhen People’s Hospital, Second Clinical Medical College of Jinan University, First Clinical Medical College of Southern University of Science and Technology, Shenzhen, Guangdong, P. R. China  \n5Application Business Division, Shandong Qilu Stem Cell Engineering Co., Ltd., Shandong, Guangdong, P. R. China  \n6 Department of Materials Science, Shenzhen MSU-BIT University, Shenzhen, Guangdong, P. R. China  \nGraphical Abstract  \nHBV infection was correlated with suppression of BMP9 expression and caused abnormal vasculature in HCC. BMP9 overexpression in HBV-infected HCC cells could promote intra-tumoural infiltration of cytotoxic lymphocytes via vascular normalisation by inhibiting the Rho-ROCK-MLC pathway, resulting in enhanced anti-PD-L1 immunotherapy. UTMD-mediated BMP9 delivery restored  \nClin. Transl. Med. 2023;13:e1247 .  \n[https://doi.org/10.1002/ctm2.1247](https://doi.org/10.1002/ctm2.1247)  \n[wileyonlinelibrary.com/journal/ctm2](wileyonlinelibrary.com/journal/ctm2)  \nHAN et al.  \nCorrespondence  \nTong Xiang, Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, SunYat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China. [Email:](Email: xiangtong@sysucc.org.cn)[ xiangtong@sysucc.org.cn](Email: xiangtong@sysucc.org.cn)  \nanti-tumour function and showed therapeutic efficacy of cytotoxic lymphocytes in combination with a PD-L1 inhibitor.  \nDOI: 10.1002/ctm2.1247  \nRESEARCH ARTICLE  \nBMP9-induced vascular normalisation improves the efficacy of immunotherapy against hepatitis B virus-associated hepatocellular carcinoma  \nYulong Han1 ,\\#  Qiuzhong Pan1 ,\\#  Zhixing Guo1,2 ,\\#  Yufei Du1  Yaojun Zhang3  Yingying Liu4  Jingjing Zhao1  Jinfeng Xu4  Jieying Yang1  Dijun Ouyang1  Yan Tang1  Qijing Wang1  Yongqiang Li1  Jia He1  Mengjuan Yang1  Hao Chen1  Chaopin Yang1  Xinyi Yang1  Jinqi You1  Yuanyuan Chen1  Minghao Ren5  Yao Zhu4, 6  Jianchuan Xia1   Tong Xiang1   \n1 Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P. R. China  \n2 Department of Ultrasound, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P. R. China  \n3 Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P. R. China  \n4 Department of Ultrasonography, Shenzhen Medical Ultrasound Engineering Center, Shenzhen People’s Hospital, Second Clinical Medical College of Jinan University, First Clinical Medical College of Southern University of Science and Technology, Shenzhen, Guangdong, P. R. China  \n5Application Business ","cbCaiiJ3seaOSJZ3","https://ap.wps.com/l/cbCaiiJ3seaOSJZ3","pdf",9861526,23,"English","# Abstract\n## Background\n## Methods\n## Results","[{\"question\":\"What problem does the study address in hepatitis B virus-associated HCC immunotherapy?\",\"answer\":\"The study addresses limited effectiveness of immune checkpoint blocking by focusing on the reduced trafficking of cytotoxic lymphocytes into tumours, which is critical for successful ICB.\"},{\"question\":\"How was BMP9 related to vascular normalisation identified and validated?\",\"answer\":\"BMP9 was identified via RNA-seq analysis using Cytoscape, and then validated using clinical specimens and Gene Expression Omnibus (GEO) datasets for HCC.\"},{\"question\":\"What delivery approach and therapeutic combination were tested?\",\"answer\":\"An ultrasound-targeted microbubble destruction (UTMD)-mediated BMP9 delivery strategy was used to normalise tumour vasculature, and therapeutic efficacy was evaluated with cytotoxic lymphocytes (NK cells) combined with a PD-L1 antibody in human cancer xenografts.\"}]","BMP9-induced vascular normalisation improves the efficacy of immunotherapy against hepatitis B virus-associated hepatocellular carcinoma | PDF",1790220945,58]