89 / 2024-10-21 17:27:26

Role of Epigenomic Reprogramming in Immunotherapy Resistance of Hepatocellular Carcinoma

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

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.