DataSheet_1_Single-Cell Transcriptomic Analysis Reveals Macrophage–Tumor Crosstalk in Hepatocellular Carcinoma.docx

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.

肝细胞癌（hepatocellular carcinoma, HCC）作为最恶性的癌症之一，拥有以高度异质性为典型特征的复杂生态系统。细胞串扰已被证实对肝细胞癌的发生发展至关重要，但目前学界对肝细胞癌中的细胞通讯调控机制仍知之甚少。本研究通过分析10名肝细胞癌患者的原发性肿瘤组织（n=10）与癌旁组织（n=8）的单细胞转录组数据，发现相较于癌旁组织，原发性肿瘤免疫细胞组分中的浆细胞样树突状细胞（plasmacytoid dendritic cells, pDCs）与自然杀伤（natural killer, NK）细胞比例显著降低，而巨噬细胞比例则显著升高。进一步而言，本研究发现巨噬细胞群体与其他细胞类型间存在广泛的通讯联系，且该类通讯在原发性肿瘤中显著增强，尤其是与肝细胞癌恶性细胞之间的通讯。另外，本研究还鉴定出SPP1–CD44轴是巨噬细胞与肝细胞癌恶性细胞之间的独特互作通路。本研究针对肝细胞癌生态系统绘制的细胞通讯模式全景图谱，为免疫浸润领域的研究提供了新的见解。