Single‐Nucleus and Spatial Transcriptome Profiling Delineates the Multicellular Ecosystem in Hepatocellular Carcinoma After Hepatic Arterial Infusion Chemotherapy
Abstract Hepatic arterial infusion chemotherapy (HAIC) has emerged as a promising treatment strategy for hepatocellular carcinoma (HCC), but a detailed understanding of the multicellular ecosystem after HAIC treatment is lacking. Here, we collected tumor samples from treatment‐naïve primary and post...
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Wiley
2025-02-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202405749 |
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| author | YeXing Huang ZeFeng Du ZhiCheng Lai DongSheng Wen LiChang Huang MinKe He ZiChao Wu HuiFang Li HanYue OuYang WenChao Wu Anna Kan Ming Shi |
| author_facet | YeXing Huang ZeFeng Du ZhiCheng Lai DongSheng Wen LiChang Huang MinKe He ZiChao Wu HuiFang Li HanYue OuYang WenChao Wu Anna Kan Ming Shi |
| author_sort | YeXing Huang |
| collection | DOAJ |
| description | Abstract Hepatic arterial infusion chemotherapy (HAIC) has emerged as a promising treatment strategy for hepatocellular carcinoma (HCC), but a detailed understanding of the multicellular ecosystem after HAIC treatment is lacking. Here, we collected tumor samples from treatment‐naïve primary and post‐HAIC HCC, and integrated single‐nucleus RNA sequencing with spatial transcriptomics to characterize the tumor ecosystem in the post‐HAIC HCC. Increased fractions and enhanced cellular communication of CD4+ T, CD20+ B, and dendritic cell subtypes were identified in post‐HAIC tumors. Moreover, it is substantiated that HAIC promoted tertiary lymphoid structures (TLS) formation, and addressed the roles of TLSs as spatial niches of cellular communication. Specifically, intermediate exhausted CD8+ T cells expressing Granzyme‐K and PD‐1 (PD‐1+CD8+ Tex‐int) expanded following HAIC and exhibited a functionally antitumor phenotype. PD‐1+CD8+ Tex‐int accumulated in the TLS vicinity and disseminated throughout the tumor microenvironment, demonstrating potential as an effective biomarker for HAIC‐based treatment in HCC. This study provides valuable resources and biological insights in the cellular underpinnings of HAIC treatment. |
| format | Article |
| id | doaj-art-6e013997fc26432a825d6c9a07339240 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-6e013997fc26432a825d6c9a073392402025-02-04T13:14:54ZengWileyAdvanced Science2198-38442025-02-01125n/an/a10.1002/advs.202405749Single‐Nucleus and Spatial Transcriptome Profiling Delineates the Multicellular Ecosystem in Hepatocellular Carcinoma After Hepatic Arterial Infusion ChemotherapyYeXing Huang0ZeFeng Du1ZhiCheng Lai2DongSheng Wen3LiChang Huang4MinKe He5ZiChao Wu6HuiFang Li7HanYue OuYang8WenChao Wu9Anna Kan10Ming Shi11Department of Hepatobiliary Oncology Sun Yat‐sen University Cancer Center Guangdong Provincial Clinical Research Center for Cancer State Key Laboratory of Oncology in South China Guangzhou 510060 P. R. ChinaDepartment of Hepatobiliary Oncology Sun Yat‐sen University Cancer Center Guangdong Provincial Clinical Research Center for Cancer State Key Laboratory of Oncology in South China Guangzhou 510060 P. R. ChinaDepartment of Hepatobiliary Oncology Sun Yat‐sen University Cancer Center Guangdong Provincial Clinical Research Center for Cancer State Key Laboratory of Oncology in South China Guangzhou 510060 P. R. ChinaDepartment of Hepatobiliary Oncology Sun Yat‐sen University Cancer Center Guangdong Provincial Clinical Research Center for Cancer State Key Laboratory of Oncology in South China Guangzhou 510060 P. R. ChinaDepartment of Hepatobiliary Oncology Sun Yat‐sen University Cancer Center Guangdong Provincial Clinical Research Center for Cancer State Key Laboratory of Oncology in South China Guangzhou 510060 P. R. ChinaDepartment of Hepatobiliary Oncology Sun Yat‐sen University Cancer Center Guangdong Provincial Clinical Research Center for Cancer State Key Laboratory of Oncology in South China Guangzhou 510060 P. R. ChinaDepartment of Hepatobiliary Oncology Sun Yat‐sen University Cancer Center Guangdong Provincial Clinical Research Center for Cancer State Key Laboratory of Oncology in South China Guangzhou 510060 P. R. ChinaDepartment of Hepatobiliary Oncology Sun Yat‐sen University Cancer Center Guangdong Provincial Clinical Research Center for Cancer State Key Laboratory of Oncology in South China Guangzhou 510060 P. R. ChinaDepartment of Hepatobiliary Oncology Sun Yat‐sen University Cancer Center Guangdong Provincial Clinical Research Center for Cancer State Key Laboratory of Oncology in South China Guangzhou 510060 P. R. ChinaDepartment of Hepatobiliary Oncology Sun Yat‐sen University Cancer Center Guangdong Provincial Clinical Research Center for Cancer State Key Laboratory of Oncology in South China Guangzhou 510060 P. R. ChinaDepartment of Hepatobiliary Oncology Sun Yat‐sen University Cancer Center Guangdong Provincial Clinical Research Center for Cancer State Key Laboratory of Oncology in South China Guangzhou 510060 P. R. ChinaDepartment of Hepatobiliary Oncology Sun Yat‐sen University Cancer Center Guangdong Provincial Clinical Research Center for Cancer State Key Laboratory of Oncology in South China Guangzhou 510060 P. R. ChinaAbstract Hepatic arterial infusion chemotherapy (HAIC) has emerged as a promising treatment strategy for hepatocellular carcinoma (HCC), but a detailed understanding of the multicellular ecosystem after HAIC treatment is lacking. Here, we collected tumor samples from treatment‐naïve primary and post‐HAIC HCC, and integrated single‐nucleus RNA sequencing with spatial transcriptomics to characterize the tumor ecosystem in the post‐HAIC HCC. Increased fractions and enhanced cellular communication of CD4+ T, CD20+ B, and dendritic cell subtypes were identified in post‐HAIC tumors. Moreover, it is substantiated that HAIC promoted tertiary lymphoid structures (TLS) formation, and addressed the roles of TLSs as spatial niches of cellular communication. Specifically, intermediate exhausted CD8+ T cells expressing Granzyme‐K and PD‐1 (PD‐1+CD8+ Tex‐int) expanded following HAIC and exhibited a functionally antitumor phenotype. PD‐1+CD8+ Tex‐int accumulated in the TLS vicinity and disseminated throughout the tumor microenvironment, demonstrating potential as an effective biomarker for HAIC‐based treatment in HCC. This study provides valuable resources and biological insights in the cellular underpinnings of HAIC treatment.https://doi.org/10.1002/advs.202405749hepatic arterial infusion chemotherapyhepatocellular carcinomasingle‐cell Multi‐Omicstertiary lymphoid structurestumor immunology |
| spellingShingle | YeXing Huang ZeFeng Du ZhiCheng Lai DongSheng Wen LiChang Huang MinKe He ZiChao Wu HuiFang Li HanYue OuYang WenChao Wu Anna Kan Ming Shi Single‐Nucleus and Spatial Transcriptome Profiling Delineates the Multicellular Ecosystem in Hepatocellular Carcinoma After Hepatic Arterial Infusion Chemotherapy Advanced Science hepatic arterial infusion chemotherapy hepatocellular carcinoma single‐cell Multi‐Omics tertiary lymphoid structures tumor immunology |
| title | Single‐Nucleus and Spatial Transcriptome Profiling Delineates the Multicellular Ecosystem in Hepatocellular Carcinoma After Hepatic Arterial Infusion Chemotherapy |
| title_full | Single‐Nucleus and Spatial Transcriptome Profiling Delineates the Multicellular Ecosystem in Hepatocellular Carcinoma After Hepatic Arterial Infusion Chemotherapy |
| title_fullStr | Single‐Nucleus and Spatial Transcriptome Profiling Delineates the Multicellular Ecosystem in Hepatocellular Carcinoma After Hepatic Arterial Infusion Chemotherapy |
| title_full_unstemmed | Single‐Nucleus and Spatial Transcriptome Profiling Delineates the Multicellular Ecosystem in Hepatocellular Carcinoma After Hepatic Arterial Infusion Chemotherapy |
| title_short | Single‐Nucleus and Spatial Transcriptome Profiling Delineates the Multicellular Ecosystem in Hepatocellular Carcinoma After Hepatic Arterial Infusion Chemotherapy |
| title_sort | single nucleus and spatial transcriptome profiling delineates the multicellular ecosystem in hepatocellular carcinoma after hepatic arterial infusion chemotherapy |
| topic | hepatic arterial infusion chemotherapy hepatocellular carcinoma single‐cell Multi‐Omics tertiary lymphoid structures tumor immunology |
| url | https://doi.org/10.1002/advs.202405749 |
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