Single-cell RNA sequencing reveals intratumoral heterogeneity and multicellular community in primary hepatocellular carcinoma underlying microvascular invasion

作者：Zhuoya Sun, Biao Gao, Lai Song, Biying Wang, Junfeng Li, Hao Jiang, X. H. Li, Yang Yu, Zishan Zhou, Zizhong Yang, Xiaohui Sun, Tianyu Jiao, Xiao Ling Zhao, Shichun Lu, Shun-chang Jiao · 发表于：Heliyon · 年份：2024 · DOI：10.1016/j.heliyon.2024.e37233 · 被引用次数：6 · 研究领域：Single-cell and spatial transcriptomics、Cancer Immunotherapy and Biomarkers、Ferroptosis and cancer prognosis

Background Microvascular invasion (MVI) is associated with an unfavorable prognosis and early recurrence of hepatocellular carcinoma (HCC), which is the crucial pathological hallmark of immunotherapy. While microvascular invasion (MVI) in hepatocellular carcinoma (HCC) currently lacks a detailed single-cell analysis of the tumor microenvironment (TME), it holds significant promise for immunotherapy using immune checkpoint inhibitors (ICI). Methods We performed single-cell RNA sequencing (scRNA-seq) on 3 MVI positive (MVIP) and 14 MVI-negative (MVIN) tumor tissues, as well as their paired adjacent non-tumoral tissues. Results We identified SPP1 + macrophages and CD4 + proliferative T cells as intertumoral populations critical for the formation of cold tumors and immunosuppressive environments in MVI-positive patients and verified their prognostic value in correlation with MVIP HCC patients. Additionally, we identified SPP1 + dominated interactions between SPP1 + macrophages and the immunosuppressive T population as contributors to MVI destruction and tumorigenesis. Conclusions We provide a comprehensive single-cell atlas of HCC patients with MVI, shedding light on the immunosuppressive ecosystem and upregulated signaling associated with MVI. These findings demonstrate that intercellular mechanisms drive MVI and provide a potential immunotherapeutic target for HCC patients with HCC and underlying MVI.