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


ABSTRACT: 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.

SUBMITTER: Wang X 

PROVIDER: S-EPMC10839686 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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

Wang Xiaoshuang X   Zhou Yan Y   Wu Zhongen Z   Xie Cao C   Xu Weiqi W   Zhou Qingtong Q   Yang Dehua D   Zhu Di D   Wang Ming-Wei MW   Wang Lu L  

iScience 20240112 2


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<sup>+</sup> and dysfunctional CD8<sup>+</sup> T cells were enriched in LM along with low antigen presentation. We also found that macrophages were associated with the tumor infiltrating CD  ...[more]

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