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

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.