Single-Cell Transcriptomic Analysis Reveals Macrophage–Tumor Crosstalk in Hepatocellular Carcinoma

As one of the most malignant cancer, hepatocellular carcinoma (HCC) has a complex ecosystem featured by high heterogeneity. Cell crosstalk is demonstrated to be critical for HCC development. However, the cell communication orchestration in HCC remains largely unknown. Here, by analyzing the single-cell transcriptomes of the primary tumor tissues (n = 10) and tumor-adjacent tissues (n = 8) derived from 10 patients with HCC, we found that the proportions of plasmacytoid dendritic cells (pDCs) and natural killer (NK) cells were reduced and that the proportion of macrophages was increased in the immune component of the primary tumor, compared with those in the tumor-adjacent tissue. Furthermore, we found widespread communication between macrophage populations and other cell types, and this communication was remarkably strengthened in the primary tumor, especially with HCC malignant cells. In addition, the SPP1–CD44 axis was identified as a unique interaction between macrophages and HCC malignant cells. Our comprehensive portrait of cell communication patterns over the HCC ecosystem reveals further insights into immune infiltration.