肝细胞癌（HCC）的肿瘤微环境异质性对空间单细胞分辨率的影响尚不清楚。在这里，我们通过索引进行联合检测，以分析具有 36 个生物标志物的 401 个 HCC 样本的空间异质性。通过解析肝癌的空间肿瘤生态系统，我们确定了具有不同预后以及基因组和分子特征的空间模式，并揭示了波形蛋白（VIM）高巨噬细胞的进展作用。八个独立队列的整合分析表明，VIMhigh 巨噬细胞和调节性 T 细胞的空间共存可促进肿瘤进展并有利于免疫治疗。功能研究进一步表明，VIMhigh 巨噬细胞通过机械地增加 IL-1β 的分泌来增强调节性 T 细胞的免疫抑制活性。我们的数据提供了对肿瘤微环境结构异质性的深入见解，并揭示了 VIMhigh 巨噬细胞在 HCC 进展过程中的关键作用，这具有个性化癌症预防和药物发现的潜力，并强化了解决癌症治疗的空间信息特征的需求。© 2024 . 作者获得 Springer Nature America, Inc. 的独家许可。

Tumor microenvironment heterogeneity in hepatocellular carcinoma (HCC) on a spatial single-cell resolution is unclear. Here, we conducted co-detection by indexing to profile the spatial heterogeneity of 401 HCC samples with 36 biomarkers. By parsing the spatial tumor ecosystem of liver cancer, we identified spatial patterns with distinct prognosis and genomic and molecular features, and unveiled the progressive role of vimentin (VIM)high macrophages. Integration analysis with eight independent cohorts demonstrated that the spatial co-occurrence of VIMhigh macrophages and regulatory T cells promotes tumor progression and favors immunotherapy. Functional studies further demonstrated that VIMhigh macrophages enhance the immune-suppressive activity of regulatory T cells by mechanistically increasing the secretion of interleukin-1β. Our data provide deep insights into the heterogeneity of tumor microenvironment architecture and unveil the critical role of VIMhigh macrophages during HCC progression, which holds potential for personalized cancer prevention and drug discovery and reinforces the need to resolve spatial-informed features for cancer treatment.© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.