Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Cell Rep Med. 2024 Feb 20;5(2):101394. doi: 10.1016/j.xcrm.2024.101394. Epub 2024 Jan 26.
A tumor ecosystem constantly evolves over time in the face of immune predation or therapeutic intervention, resulting in treatment failure and tumor progression. Here, we present a single-cell transcriptome-based strategy to determine the evolution of longitudinal tumor biopsies from liver cancer patients by measuring cellular lineage and ecology. We construct a lineage and ecological score as joint dynamics of tumor cells and their microenvironments. Tumors may be classified into four main states in the lineage-ecological space, which are associated with clinical outcomes. Analysis of longitudinal samples reveals the evolutionary trajectory of tumors in response to treatment. We validate the lineage-ecology-based scoring system in predicting clinical outcomes using bulk transcriptomic data of additional cohorts of 716 liver cancer patients. Our study provides a framework for monitoring tumor evolution in response to therapeutic intervention.
肿瘤生态系统在面临免疫捕食或治疗干预时会随着时间不断演变，导致治疗失败和肿瘤进展。在这里，我们提出了一种基于单细胞转录组的策略，通过测量细胞谱系和生态来确定肝癌患者纵向活检肿瘤的演变。我们构建了一个谱系和生态评分，作为肿瘤细胞及其微环境的联合动力学。肿瘤可以在谱系-生态空间中分为四个主要状态，这些状态与临床结果相关。对纵向样本的分析揭示了肿瘤对治疗的反应的进化轨迹。我们使用另外 716 例肝癌患者的大量转录组数据验证了基于谱系-生态的评分系统在预测临床结果中的作用。我们的研究为监测治疗干预反应中的肿瘤进化提供了一个框架。
