Yiran Li, Ziyu Xun, Junyu Long, Huishan Sun, Xu Yang, Yanyu Wang, Yunchao Wang, Jingnan Xue, Nan Zhang, Junwei Zhang, Jin Bian, Jie Shi, Xiaobo Yang, Hanping Wang, Haitao Zhao
{"title":"人类肝胆管癌图谱中的免疫抑制和表型可塑性。","authors":"Yiran Li, Ziyu Xun, Junyu Long, Huishan Sun, Xu Yang, Yanyu Wang, Yunchao Wang, Jingnan Xue, Nan Zhang, Junwei Zhang, Jin Bian, Jie Shi, Xiaobo Yang, Hanping Wang, Haitao Zhao","doi":"10.21037/hbsn-23-400","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Hepatocholangiocarcinoma (H-ChC) has the clinicopathological features of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) and is a more aggressive subtype of primary hepatic carcinoma than HCC or iCCA.</p><p><strong>Methods: </strong>We sequenced 91,112 single-cell transcriptomes from 16 human samples to elucidate the molecular mechanisms underlying the coexistence of HCC and iCCA components in H-ChC.</p><p><strong>Results: </strong>We observed two molecular subtypes of H-ChC at the whole-transcriptome level (CHP and CIP), where a metabolically active tumour cell subpopulation enriched in CHP was characterized by a cellular pre-differentiation property. To define the heterogeneity of tumours and their associated microenvironments, we observe greater tumour diversity in H-ChC than HCC and iCCA. H-ChC exhibits weaker immune cell infiltration and greater CD8<sup>+</sup> exhausted T cell (Tex) dysfunction than HCC and iCCA. Then we defined two broad cell states of 6,852 CD8<sup>+</sup> Tex cells: GZMK<sup>+</sup> CD8<sup>+</sup> Tex cells and terminal CD8<sup>+</sup> Tex cells. GZMK<sup>+</sup> CD8<sup>+</sup> Tex cells exhibited higher infiltration of after treatment in H-ChC, the effector scores and expression of the immune checkpoints of them greatly increased after immunotherapy, which indicated that H-ChC might be more sensitive than HCC or iCCA to immunotherapy.</p><p><strong>Conclusions: </strong>In this paper, H-ChC was explored, hoping to contribute to the study of mixed tumours in other cancers.</p>","PeriodicalId":12878,"journal":{"name":"Hepatobiliary surgery and nutrition","volume":"13 4","pages":"586-603"},"PeriodicalIF":6.1000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11336540/pdf/","citationCount":"0","resultStr":"{\"title\":\"Immunosuppression and phenotypic plasticity in an atlas of human hepatocholangiocarcinoma.\",\"authors\":\"Yiran Li, Ziyu Xun, Junyu Long, Huishan Sun, Xu Yang, Yanyu Wang, Yunchao Wang, Jingnan Xue, Nan Zhang, Junwei Zhang, Jin Bian, Jie Shi, Xiaobo Yang, Hanping Wang, Haitao Zhao\",\"doi\":\"10.21037/hbsn-23-400\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Hepatocholangiocarcinoma (H-ChC) has the clinicopathological features of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) and is a more aggressive subtype of primary hepatic carcinoma than HCC or iCCA.</p><p><strong>Methods: </strong>We sequenced 91,112 single-cell transcriptomes from 16 human samples to elucidate the molecular mechanisms underlying the coexistence of HCC and iCCA components in H-ChC.</p><p><strong>Results: </strong>We observed two molecular subtypes of H-ChC at the whole-transcriptome level (CHP and CIP), where a metabolically active tumour cell subpopulation enriched in CHP was characterized by a cellular pre-differentiation property. To define the heterogeneity of tumours and their associated microenvironments, we observe greater tumour diversity in H-ChC than HCC and iCCA. H-ChC exhibits weaker immune cell infiltration and greater CD8<sup>+</sup> exhausted T cell (Tex) dysfunction than HCC and iCCA. Then we defined two broad cell states of 6,852 CD8<sup>+</sup> Tex cells: GZMK<sup>+</sup> CD8<sup>+</sup> Tex cells and terminal CD8<sup>+</sup> Tex cells. GZMK<sup>+</sup> CD8<sup>+</sup> Tex cells exhibited higher infiltration of after treatment in H-ChC, the effector scores and expression of the immune checkpoints of them greatly increased after immunotherapy, which indicated that H-ChC might be more sensitive than HCC or iCCA to immunotherapy.</p><p><strong>Conclusions: </strong>In this paper, H-ChC was explored, hoping to contribute to the study of mixed tumours in other cancers.</p>\",\"PeriodicalId\":12878,\"journal\":{\"name\":\"Hepatobiliary surgery and nutrition\",\"volume\":\"13 4\",\"pages\":\"586-603\"},\"PeriodicalIF\":6.1000,\"publicationDate\":\"2024-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11336540/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Hepatobiliary surgery and nutrition\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.21037/hbsn-23-400\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/12 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hepatobiliary surgery and nutrition","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21037/hbsn-23-400","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/12 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
Immunosuppression and phenotypic plasticity in an atlas of human hepatocholangiocarcinoma.
Background: Hepatocholangiocarcinoma (H-ChC) has the clinicopathological features of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) and is a more aggressive subtype of primary hepatic carcinoma than HCC or iCCA.
Methods: We sequenced 91,112 single-cell transcriptomes from 16 human samples to elucidate the molecular mechanisms underlying the coexistence of HCC and iCCA components in H-ChC.
Results: We observed two molecular subtypes of H-ChC at the whole-transcriptome level (CHP and CIP), where a metabolically active tumour cell subpopulation enriched in CHP was characterized by a cellular pre-differentiation property. To define the heterogeneity of tumours and their associated microenvironments, we observe greater tumour diversity in H-ChC than HCC and iCCA. H-ChC exhibits weaker immune cell infiltration and greater CD8+ exhausted T cell (Tex) dysfunction than HCC and iCCA. Then we defined two broad cell states of 6,852 CD8+ Tex cells: GZMK+ CD8+ Tex cells and terminal CD8+ Tex cells. GZMK+ CD8+ Tex cells exhibited higher infiltration of after treatment in H-ChC, the effector scores and expression of the immune checkpoints of them greatly increased after immunotherapy, which indicated that H-ChC might be more sensitive than HCC or iCCA to immunotherapy.
Conclusions: In this paper, H-ChC was explored, hoping to contribute to the study of mixed tumours in other cancers.
期刊介绍:
Hepatobiliary Surgery and Nutrition (HBSN) is a bi-monthly, open-access, peer-reviewed journal (Print ISSN: 2304-3881; Online ISSN: 2304-389X) since December 2012. The journal focuses on hepatopancreatobiliary disease and nutrition, aiming to present new findings and deliver up-to-date, practical information on diagnosis, prevention, and clinical investigations. Areas of interest cover surgical techniques, clinical and basic research, transplantation, therapies, NASH, NAFLD, targeted drugs, gut microbiota, metabolism, cancer immunity, genomics, and nutrition and dietetics. HBSN serves as a valuable resource for professionals seeking insights into diverse aspects of hepatobiliary surgery and nutrition.