肿瘤生态系统的适应度和生存能力受其细胞的空间组织的影响。我们旨在使用空间分辨多重免疫荧光成像方法，研究异质肝癌肿瘤微环境的结构、架构和细胞间动态。我们在泰国患者（TIGER-LC）的68例肝细胞癌（HCC）活检标本上进行了索引共检测（CODEX）多重免疫荧光成像，作为发现队列，并在中国患者（LCI）的其他190例HCC活检标本上验证了结果。我们分割和注释了TIGER-LC队列的117,270个细胞和LCI队列的465,632个细胞。我们观察到TIGER-LC患者被分为四个不同的（IC1、IC2、IC3、IC4）肿瘤免疫细胞相互作用模式的群体。此外，IC2和IC4患者的总生存率明显优于IC1和IC3患者。值得注意的是，肿瘤和CD8+ T细胞的相互作用在IC2中得到了显著丰富，该组患者的预后最佳。在TIGER-LC和LCI队列中，肿瘤和CD8+ T细胞的紧密接触是患者预后的强有力预测因子。我们利用了51例HCC案例中的总转录组数据来确定我们分类亚型的肿瘤特异性基因表达特征。此外，我们观察到在HCC中，作为整体免疫浸润的测量，免疫空间邻域的存在与更好的患者预后相关。肝癌的高度多重成像分析揭示了肿瘤免疫细胞的异质性，以及在肿瘤和CD8 + T细胞相互作用等空间上下文中，可能预测患者生存。版权所有2013,美国肝病研究协会。

The fitness and viability of a tumor ecosystem are influenced by the spatial organization of its cells. We aimed to study the structure, architecture, and cell-cell dynamics of the heterogenous liver cancer tumor microenvironment using spatially resolved multiplexed imaging.We performed co-detection by indexing (CODEX) multiplexed immunofluorescence imaging on 68 hepatocellular carcinoma (HCC) biopsies from Thai patients (TIGER-LC) as a discovery cohort, and then validated the results in an additional 190 HCC biopsies from Chinese patients (LCI). We segmented and annotated 117,270 and 465,632 cells from the TIGER-LC and LCI cohorts, respectively. We observed four groups of TIGER-LC patients (IC1, IC2, IC3, IC4) with distinct tumor-immune cellular interaction patterns. In addition, patients from IC2 and IC4 had much better overall survival than those from IC1 and IC3. Noticeably, tumor and CD8+ T cell interactions were strongly enriched in IC2, the group with the best patient outcomes. Close proximity between tumor and CD8+ T cells was a strong predictor of patient outcome in both the TIGER-LC and the LCI cohorts. Bulk transcriptomic data from 51 of the 68 HCC cases was utilized to determine tumor-specific gene expression features of our classified subtypes. Moreover, we observed that the presence of immune spatial neighborhoods in HCC as a measure of overall immune infiltration is linked to better patient prognosis.Highly multiplexed imaging analysis of liver cancer reveals tumor-immune cellular heterogeneity within spatial contexts, such as tumor and CD8+ T cell interactions, which may predict patient survival.Copyright © 2023 American Association for the Study of Liver Diseases.