Immunosuppression and phenotypic plasticity in an atlas of human hepatocholangiocarcinoma  

作　　者：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 

机构地区：[1]State Key Laboratory of Complex Severe and Rare Diseases,Department of Liver Surgery,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College(CAMS&PUMC),Beijing,China [2]Division of Pulmonary and Critical Care Medicine,State Key Laboratory of Complex Severe and Rare Diseases,Chinese Academy of Medical Sciences and Peking Union Medical College(CAMS&PUMC),Beijing,China

出　　处：《Hepatobiliary Surgery and Nutrition》2024年第4期586-603,I0002-I0014,共31页肝胆外科与营养（英文）

基　　金：CAMS Innovation Fund for Medical Sciences(CIFMS)(2021-I2M-1-061 and 2021-1-I2M-003);CSCO-hengrui Cancer Research Fund(Y-HR2019-0239);CSCO-MSD Cancer Research Fund(Y-MSDZD2021-0213);National Ten-thousand Talent Program(to J.L.);Young Scientists Fund of the National Natural Science Foundation of China(82303720);Beijing Natural Science Foundation(7234381);Fundamental Research Funds for the Central Universities(3332023011 to J.L.).

摘　　要：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.

关 键 词：Hepatocholangiocarcinoma(H-ChC) biphenotypic PLASTICITY CD8+Tex cells IMMUNOSUPPRESSION 

分 类 号：R735.8[医药卫生—肿瘤]