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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.