Single-cell transcriptomics reveals the role of antigen presentation in liver metastatic breast cancer

Summary: Liver metastasis (LM) is the primary cause of cancer-related mortality in late-stage breast cancer (BC) patients. Here we report an in-depth analysis of the transcriptional landscape of LM of 11 patients with secondary hepatic carcinoma at single-cell resolution. Our study reveals that term...

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Main Authors: Xiaoshuang Wang, Yan Zhou, Zhongen Wu, Cao Xie, Weiqi Xu, Qingtong Zhou, Dehua Yang, Di Zhu, Ming-Wei Wang, Lu Wang
Format: Article
Language:English
Published: Elsevier 2024-02-01
Series:iScience
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004224001172
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author Xiaoshuang Wang
Yan Zhou
Zhongen Wu
Cao Xie
Weiqi Xu
Qingtong Zhou
Dehua Yang
Di Zhu
Ming-Wei Wang
Lu Wang
author_facet Xiaoshuang Wang
Yan Zhou
Zhongen Wu
Cao Xie
Weiqi Xu
Qingtong Zhou
Dehua Yang
Di Zhu
Ming-Wei Wang
Lu Wang
author_sort Xiaoshuang Wang
collection DOAJ
description Summary: Liver metastasis (LM) is the primary cause of cancer-related mortality in late-stage breast cancer (BC) patients. Here we report an in-depth analysis of the transcriptional landscape of LM of 11 patients with secondary hepatic carcinoma at single-cell resolution. Our study reveals that terminally exhausted CD4+ and dysfunctional CD8+ T cells were enriched in LM along with low antigen presentation. We also found that macrophages were associated with the tumor infiltrating CD4+ T cells, while FCN3+ macrophages, type 1 conventional dendritic cells (cDC1) and LAMP3+ DC regulated T cell functions, probably via antigen processing and presentation. Major histocompatibility complex expression in FCN3+ macrophage, cDC1 and LAMP3+ DC was reduced in LM compared to those in normal tissues and primary BC. Malfunctioned antigen presentation in these cells is linked to a worse prognosis in invasive BC and hepatocellular carcinoma. Our results provide valuable insights into the role of tumor infiltrating T cells in LM.
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spelling doaj.art-bc577b3297f74819abecd8602dd4624c2024-01-27T06:55:51ZengElsevieriScience2589-00422024-02-01272108896Single-cell transcriptomics reveals the role of antigen presentation in liver metastatic breast cancerXiaoshuang Wang0Yan Zhou1Zhongen Wu2Cao Xie3Weiqi Xu4Qingtong Zhou5Dehua Yang6Di Zhu7Ming-Wei Wang8Lu Wang9Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaThe National Center for Drug Screening and the State Key Laboratory of Chemical Biology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), Shanghai 201203, ChinaSchool of Basic Medical Sciences, Fudan University, Shanghai 200032, ChinaSchool of Pharmacy, Fudan University, Shanghai 201203, ChinaFudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai 200032, ChinaSchool of Basic Medical Sciences, Fudan University, Shanghai 200032, ChinaThe National Center for Drug Screening and the State Key Laboratory of Chemical Biology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), Shanghai 201203, ChinaSchool of Basic Medical Sciences, Fudan University, Shanghai 200032, China; Minhang Hospital and Shanghai Medical College, Fudan University, Shanghai 201100, China; Corresponding authorSchool of Basic Medical Sciences, Fudan University, Shanghai 200032, China; Research Center for Deepsea Bioresources, Sanya, Hainan 572025, China; Corresponding authorFudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai 200032, China; Corresponding authorSummary: Liver metastasis (LM) is the primary cause of cancer-related mortality in late-stage breast cancer (BC) patients. Here we report an in-depth analysis of the transcriptional landscape of LM of 11 patients with secondary hepatic carcinoma at single-cell resolution. Our study reveals that terminally exhausted CD4+ and dysfunctional CD8+ T cells were enriched in LM along with low antigen presentation. We also found that macrophages were associated with the tumor infiltrating CD4+ T cells, while FCN3+ macrophages, type 1 conventional dendritic cells (cDC1) and LAMP3+ DC regulated T cell functions, probably via antigen processing and presentation. Major histocompatibility complex expression in FCN3+ macrophage, cDC1 and LAMP3+ DC was reduced in LM compared to those in normal tissues and primary BC. Malfunctioned antigen presentation in these cells is linked to a worse prognosis in invasive BC and hepatocellular carcinoma. Our results provide valuable insights into the role of tumor infiltrating T cells in LM.http://www.sciencedirect.com/science/article/pii/S2589004224001172ImmunologyCancerTranscriptomics
spellingShingle Xiaoshuang Wang
Yan Zhou
Zhongen Wu
Cao Xie
Weiqi Xu
Qingtong Zhou
Dehua Yang
Di Zhu
Ming-Wei Wang
Lu Wang
Single-cell transcriptomics reveals the role of antigen presentation in liver metastatic breast cancer
iScience
Immunology
Cancer
Transcriptomics
title Single-cell transcriptomics reveals the role of antigen presentation in liver metastatic breast cancer
title_full Single-cell transcriptomics reveals the role of antigen presentation in liver metastatic breast cancer
title_fullStr Single-cell transcriptomics reveals the role of antigen presentation in liver metastatic breast cancer
title_full_unstemmed Single-cell transcriptomics reveals the role of antigen presentation in liver metastatic breast cancer
title_short Single-cell transcriptomics reveals the role of antigen presentation in liver metastatic breast cancer
title_sort single cell transcriptomics reveals the role of antigen presentation in liver metastatic breast cancer
topic Immunology
Cancer
Transcriptomics
url http://www.sciencedirect.com/science/article/pii/S2589004224001172
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