肝细胞癌（HCC）检查点免疫治疗反应的决定因素仍然知之甚少。肿瘤微环境 (TME) 中免疫反应的组织预计将控制免疫治疗结果，但空间免疫类型的定义仍然不明确。我们假设空间免疫网络架构的反卷积可以识别 HCC 中临床相关的免疫类型。我们进行了高度多重成像质量对 101 名患者的 HCC 组织进行细胞计数。我们在一个发现和验证队列中进行了深入的空间单细胞分析，以解开 HCC 免疫结构异质性的决定因素，并开发了一个空间免疫分类，该分类经过测试用于预测免疫检查点抑制剂 (ICI) 治疗。生物信息学分析鉴定出 HCC TME 中的 23 种主要免疫细胞、基质细胞、实质细胞和肿瘤细胞类型。基于免疫细胞空间相互作用的无监督邻域检测确定了三种免疫结构，其中免疫细胞和免疫检查点的参与程度不同，以 CD8 T 细胞、骨髓免疫细胞或 B 和 CD4 T 细胞为主。我们使用这些来定义三种主要的空间 HCC 免疫类型，反映更高水平的肿瘤内免疫细胞组织：耗尽型、区室化型和富集型。 ICI 治疗下的无进展生存期在空间免疫类型之间存在显着差异，富集患者的生存期有所改善。在肿瘤内异质性的患者中，一个富集区域的存在决定了长期生存。© 作者（或其雇主）2024。CC BY 允许重复使用。英国医学杂志出版。

The determinants of the response to checkpoint immunotherapy in hepatocellular carcinoma (HCC) remain poorly understood. The organisation of the immune response in the tumour microenvironment (TME) is expected to govern immunotherapy outcomes but spatial immunotypes remain poorly defined.We hypothesised that the deconvolution of spatial immune network architectures could identify clinically relevant immunotypes in HCC.We conducted highly multiplexed imaging mass cytometry on HCC tissues from 101 patients. We performed in-depth spatial single-cell analysis in a discovery and validation cohort to deconvolute the determinants of the heterogeneity of HCC immune architecture and develop a spatial immune classification that was tested for the prediction of immune checkpoint inhibitor (ICI) therapy.Bioinformatic analysis identified 23 major immune, stroma, parenchymal and tumour cell types in the HCC TME. Unsupervised neighbourhood detection based on the spatial interaction of immune cells identified three immune architectures with differing involvement of immune cells and immune checkpoints dominated by either CD8 T-cells, myeloid immune cells or B- and CD4 T-cells. We used these to define three major spatial HCC immunotypes that reflect a higher level of intratumour immune cell organisation: depleted, compartmentalised and enriched. Progression-free survival under ICI therapy differed significantly between the spatial immune types with improved survival of enriched patients. In patients with intratumour heterogeneity, the presence of one enriched area governed long-term survival.© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.