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Abstract：
OBJECTIVE: Metastasis is the leading cause of mortality in hepatocellular carcinoma (HCC). The metastasis-associated immune signature in HCC is worth exploring.
METHODS: Bioinformatic analysis was conducted based on the single-cell transcriptome data derived from HCC patients in different stages. Cellular composition, pseudotime state transition, and cell-cell interaction were further analyzed and verified.
RESULTS: Generally, HCC with metastasis exhibited suppressive immune microenvironment, while HCC without metastasis exhibited active immune microenvironment. Concretely, effector regulatory T cells (eTregs) were found to be enriched in HCC with metastasis. PHLDA1 was identified as one of exhaustion-specific genes and verified to be associated with worse prognosis in HCC patients. Moreover, A novel cluster of CCR7+ dendritic cells (DCs) was identified with high expression of maturation and migration marker genes. Pseudotime analysis showed that inhibition of differentiation occurred in CCR7+ DCs rather than cDC1 in HCC with metastasis. Furthermore, interaction analysis showed that the reduction of CCR7+ DCs lead to impaired CCR7/CCL19 interaction in HCC with metastasis.
CONCLUSIONS: HCC with metastasis exhibited upregulation of exhaustion-specific genes of eTregs and inhibition of CCL signal of a novel DC cluster, which added new dimensions to the immune landscape and provided new immune therapeutic targets in advanced HCC.
METHODS: Bioinformatic analysis was conducted based on the single-cell transcriptome data derived from HCC patients in different stages. Cellular composition, pseudotime state transition, and cell-cell interaction were further analyzed and verified.
RESULTS: Generally, HCC with metastasis exhibited suppressive immune microenvironment, while HCC without metastasis exhibited active immune microenvironment. Concretely, effector regulatory T cells (eTregs) were found to be enriched in HCC with metastasis. PHLDA1 was identified as one of exhaustion-specific genes and verified to be associated with worse prognosis in HCC patients. Moreover, A novel cluster of CCR7+ dendritic cells (DCs) was identified with high expression of maturation and migration marker genes. Pseudotime analysis showed that inhibition of differentiation occurred in CCR7+ DCs rather than cDC1 in HCC with metastasis. Furthermore, interaction analysis showed that the reduction of CCR7+ DCs lead to impaired CCR7/CCL19 interaction in HCC with metastasis.
CONCLUSIONS: HCC with metastasis exhibited upregulation of exhaustion-specific genes of eTregs and inhibition of CCL signal of a novel DC cluster, which added new dimensions to the immune landscape and provided new immune therapeutic targets in advanced HCC.
摘要：
目的：转移是肝细胞癌（HCC）死亡的主要原因。肝癌转移相关的免疫特征值得探讨。
方法：基于来自不同阶段的HCC患者的单细胞转录组数据进行生物信息学分析。细胞组成，伪时间状态转换，细胞间相互作用进行了进一步分析和验证。
结果：一般来说，肝癌转移表现出抑制性免疫微环境，而无转移的HCC表现出活跃的免疫微环境。具体而言,发现效应调节性T细胞（eTregs）在具有转移的HCC中富集。PHLDA1被鉴定为耗竭特异性基因之一，并被证实与HCC患者预后较差有关。此外，鉴定了具有成熟和迁移标记基因高表达的新型CCR7树突状细胞（DC）簇。假时间分析表明，在转移的HCC中，CCR7DC而不是cDC1发生分化抑制。此外，相互作用分析表明，CCR7+DCs的减少导致HCC转移中CCR7/CCL19相互作用受损。
结论：具有转移的HCC表现出eTregs的耗竭特异性基因的上调和新型DC簇的CCL信号的抑制，这为晚期HCC的免疫前景增加了新的维度，并提供了新的免疫治疗靶点。
方法：基于来自不同阶段的HCC患者的单细胞转录组数据进行生物信息学分析。细胞组成，伪时间状态转换，细胞间相互作用进行了进一步分析和验证。
结果：一般来说，肝癌转移表现出抑制性免疫微环境，而无转移的HCC表现出活跃的免疫微环境。具体而言,发现效应调节性T细胞（eTregs）在具有转移的HCC中富集。PHLDA1被鉴定为耗竭特异性基因之一，并被证实与HCC患者预后较差有关。此外，鉴定了具有成熟和迁移标记基因高表达的新型CCR7树突状细胞（DC）簇。假时间分析表明，在转移的HCC中，CCR7DC而不是cDC1发生分化抑制。此外，相互作用分析表明，CCR7+DCs的减少导致HCC转移中CCR7/CCL19相互作用受损。
结论：具有转移的HCC表现出eTregs的耗竭特异性基因的上调和新型DC簇的CCL信号的抑制，这为晚期HCC的免疫前景增加了新的维度，并提供了新的免疫治疗靶点。
