Immunosuppression and Phenotypic Plasticity in an Atlas of Human Hepatocholangiocarcinoma

Overview

Journal Hepatobiliary Surg Nutr

Publisher AME Publishing Company

Date 2024 Aug 23

PMID 39175731

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

Affiliations

Soon will be listed here.

Abstract

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.

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