人类肝胆管癌图谱中的免疫抑制和表型可塑性。

IF 6.1 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Hepatobiliary surgery and nutrition Pub Date : 2024-08-01 Epub Date: 2024-01-12 DOI:10.21037/hbsn-23-400
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
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引用次数: 0

摘要

背景:肝胆管癌(H-ChC)具有肝细胞癌(HCC)和肝内胆管癌(iCCA)的临床病理特征,是比HCC或iCCA更具侵袭性的原发性肝癌亚型:我们对16份人体样本的91112个单细胞转录组进行了测序,以阐明H-ChC中HCC和iCCA成分共存的分子机制:我们在全转录组水平上观察到了H-ChC的两种分子亚型(CHP和CIP),其中富含CHP的代谢活跃的肿瘤细胞亚群具有细胞预分化特性。为了确定肿瘤及其相关微环境的异质性,我们观察到 H-ChC 的肿瘤多样性高于 HCC 和 iCCA。与 HCC 和 iCCA 相比,H-ChC 的免疫细胞浸润更弱,CD8+ T 细胞(Tex)功能障碍更严重。然后,我们对 6,852 个 CD8+ Tex 细胞定义了两种广泛的细胞状态:GZMK+ CD8+ Tex细胞和终末CD8+ Tex细胞。GZMK+ CD8+ Tex细胞在H-ChC治疗后表现出更高的浸润性,其效应得分和免疫检查点的表达在免疫治疗后大大增加,这表明H-ChC可能比HCC或iCCA对免疫治疗更敏感:本文对H-ChC进行了探讨,希望对其他癌症的混合瘤研究有所帮助。
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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.

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来源期刊
自引率
10.00%
发文量
392
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.
期刊最新文献
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