Investigating the Role of HDAC8 in CD4 +T Cells

Abstract T cell exclusion restricts immune checkpoint blockade (ICB) efficacy for some hepatocellular carcinoma (HCC) patients. Epigenetic therapy provides new opportunities to rewire transcriptional programs. We have recently elucidated that pharmacological inhibition of histone deacetylase 8 (HDAC8) resulted in increased CD8 +T infiltration and enhanced ICB HCC. Moreover, this combined immunotherapy induced durable survival benefits even after tumor rechallenge accompanied by elevated memory cells (Sci Transl Med, 2021). In study, we found HDAC8 HCC tumor-bearing mice. Interestingly, knockdown did not influence the effect activation cytotoxic function, suggesting an cell-intrinsic role HDAC8. was highly expressed instead other cells. Notably, upregulated memory-related gene expression CD4 cells, but Besides, acetylation structural maintenance chromosome 3 (SMC3ac), a ring-shaped cohesin component topologically entrapping enhancers promoters which may modulate expression. inhibiting SMC3ac binding onto targeting promoter region mRNA CD4-expressing Jurkat These data suggest exerts formation through SMC3ac-mediated epigenome reprogramming thus providing insights into developing effective cancer immunotherapy. Acknowledgment: This work is supported RGC Collaborative Research Fund (C4045-18W), Li Ka Shing Foundation, TRS T11-706/18-N EpiHK.