Hepatocellular carcinoma (HCC) is one of the most prevalent cancers in Asia and the third leading cause of cancer-related deaths globally. Immune-checkpoint inhibitors (ICIs) have become a new standard-of-care for HCC but only a minority of patients currently respond, necessitating urgent development of effective combination therapies. We aim at advancing the basic understanding and precision immunotherapy of HCC through a multi-disciplinary approach. On the one hand, we apply single-cell and bulk multi-omics to understand tumor adaptation to ICIs and identify the epigenetic and transcriptional programs underlying immunotherapeutic resistance. On the other hand, we develop effective and durable mechanism-based combination immunotherapies for clinical translation. Interrogation of the molecular drivers of three-dimensional genome reprogramming may provide new therapeutic targets to improve ICI efficacy for patients with HCC.
 

immunotherapeutic resistance,HCC,3D genome organization,Multi Omics