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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Elsevier
2024-02-01
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Series: | iScience |
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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. |
first_indexed | 2024-03-08T10:29:47Z |
format | Article |
id | doaj.art-bc577b3297f74819abecd8602dd4624c |
institution | Directory Open Access Journal |
issn | 2589-0042 |
language | English |
last_indexed | 2024-03-08T10:29:47Z |
publishDate | 2024-02-01 |
publisher | Elsevier |
record_format | Article |
series | iScience |
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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