Distinct immune microenvironment of venous tumor thrombus in hepatocellular carcinoma at single-cell resolution

作者：Kaiqian Zhou, Yucheng Zhong, Minfang Song, Yun‐Fan Sun, Wei Zhu, Jianwen Cheng, Yang Xu, Zefan Zhang, Pengxiang Wang, Zheng Tang, Jian Zhou, Liye Zhang, Jia Fan, Xin‐Rong Yang · 发表于：Hepatology · 年份：2024 · DOI：10.1097/hep.0000000000001182 · 被引用次数：13 · 研究领域：Single-cell and spatial transcriptomics、Ferroptosis and cancer prognosis、Hepatocellular Carcinoma Treatment and Prognosis

BACKGROUND AND AIMS: Portal vein tumor thrombus (PVTT) worsens the prognosis of hepatocellular carcinoma by increasing intrahepatic dissemination and inducing portal vein hypertension. However, the immune characteristics of PVTT remain unclear. Therefore, this study aims to explore the immune microenvironment in PVTT. APPROACH AND RESULTS: Time-of-flight mass cytometry revealed that macrophages and monocytes were the dominant immune cell type in PVTT, with a higher proportion than in primary tumor and blood (54.1% vs. 26.3% and 9.1%, p<0.05). The differentially enriched clustering of inhibitory and regulatory immune cells in PVTT indicated an immune-suppressive environment. According to the single-cell RNA sequencing, TAM-C5AR1 was characterized by leukocyte chemotaxis and was the most common subpopulation in PVTT (36.7%). Multiplex fluorescent immunohistochemistry staining showed that the C5aR+ TAM/Mφ were enriched in PVTT compared to both the primary tumor and liver and positively correlated with C5a (r=0.559, p<0.001). Notably, THP-1 (monocyte cell line) was recruited by CSQT2 (PVTT cell line) and exhibited up-regulation of CD163, CD206, and PD-L1 upon stimulation. C5aR antagonist could reverse this. C5aR+ TAMs could also inhibit Granzyme B in CD8+ T cells. High infiltration of C5aR+ TAMs in PVTT correlated with poor differentiation (p<0.009) and was a risk factor for overall survival (p=0.003) and for reformation of PVTT after resection (p=0.007). CONCLUSIONS: TAMs, espec...