Single-cell transcriptomics reveals the role of antigen presentation in liver metastatic breast cancer
Xiaoshuang Wang, Yan Zhou, Zhongen Wu, Cao Xie, Weiqi Xu, Qingtong Zhou, Dehua Yang, Di Zhu, Ming‐Wei Wang, Lu Wang
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.