Supporting data for "Inhibition of CAF-1 histone chaperone complex triggers cytosolic DNA and dsRNA sensing pathways and induces intrinsic immunity of hepatocellular carcinoma"

Epigenetic therapy may synergize with Immune checkpoint inhibitor (ICI) in cancer immunotherapy. Herein, we unraveled the immune-modulatory role of the histone chaperone complex Chromatin assembly factor 1 (CAF-1) in hepatocellular carcinoma (HCC). In HCC patients, CAF-1 complex overexpression is associated with poor prognosis. Knockout of CAF-1 remarkably triggered replicative stress, induced chromatin instability and micronuclei formation, and suppressed HCC growth. Upon CAF-1 knockout, massive H3.1 to H3.3 histone replacement increased chromatin accessibility and activated the expression of endogenous retrovirus elements (ERVs), a phenomenon known as viral mimicry. Cytosolic micronuclei and ERVs are recognized by the STING and dsRNA viral sensing pathways, respectively. Thus, knockout of CAF-1 activated inflammatory response and immune surveillance, thereby augmenting the anti-cancer effect of immune checkpoint therapy in HCC. Our findings suggest that CAF-1 is essential for HCC development, targeting CAF-1 may awaken the anti-cancer immune response and may sensitize ICI treatment in cancer therapy.

Our studies include research data of TCGA or in-house liver cancer patients and experimental data on liver cancer cell lines.Data included raw number of experiments and figures or images obtained from machines. Raw number is in the excel file. Images and figures were in a separated folder.

表观遗传治疗可能与免疫检查点抑制剂（ICI）在癌症免疫治疗中协同作用。本研究揭示了组蛋白伴侣复合物染色质组装因子1（CAF-1）在肝细胞癌（HCC）中的免疫调节作用。在HCC患者中，CAF-1复合物的高表达与不良预后相关。CAF-1敲除显著引发复制压力，诱导染色质不稳定和微核形成，并抑制HCC的生长。CAF-1敲除后，大量H3.1至H3.3组蛋白的替代增加染色质可及性，并激活内源性逆转录病毒元件（ERVs）的表达，这一现象被称为病毒模拟。细胞质微核和ERVs分别被STING和dsRNA病毒感应途径识别。因此，CAF-1的敲除激活了炎症反应和免疫监视，从而增强HCC中免疫检查点疗法的抗肿瘤效果。我们的研究结果表明，CAF-1对于HCC的发展至关重要，靶向CAF-1可能唤醒抗肿瘤免疫反应，并可能提高癌症治疗中ICI治疗的敏感性。本研究包括来自TCGA或院内肝细胞癌患者的研究数据和肝细胞癌细胞系的实验数据。数据包括实验的原始数量和来自机器的图像或图表。原始数据位于Excel文件中。图像和图表位于单独的文件夹中。