Liver cancer remains one of the most common cancers in the world. Recent research from CUHK’s Faculty of Medicine has discovered how liver cancer cells adapt to immunotherapy, the most advanced therapy for cancer patients. The team comprising the School of Biomedical Sciences (SBS) members Prof. Alfred Cheng Sze-lok, Professor; Prof. Zhou Jingying, Assistant Professor and Dr. Xiong Zhewen, Postdoctoral Fellow and other researchers empowered immunotherapy by counteracting the resistance mechanisms of cancer cells and confirmed their clinical potential in liver cancer animal models. Research results have been published in the leading international journal Gut, which can be viewed HERE. The team is also going to commence a new Phase II clinical trial of combination immunotherapy (NCT05873244), aiming to translate the discovery into patient benefits.
Recently, immunotherapy has increasingly been given to patients in the clinic. However, checkpoint inhibitors, the most used immunotherapy in liver cancer, can only benefit approximately 20% of patients. Moreover, patients who initially respond can become resistant during treatment.
Immunotherapy-resistant liver cancer patients are associated with an immunosuppressive cold tumour microenvironment. However, the animal models commonly used in the laboratory do not reflect the complex organ-specific aspects of tumour development. Advances in modelling dynamic tumour-immune interactions are therefore critical to understand resistance mechanisms and improve immunotherapy. The new clinically relevant mouse models are instrumental in identifying and verifying actionable targets for therapeutic interventions. The team has further used their new mouse models to demonstrate the effectiveness and safety of a novel class-I HDAC drug in combination with checkpoint inhibitors.
(From left) Dr Xiong Zhewen, Postdoctoral Fellow; Prof. Alfred Cheng Sze-lok, Professor; Prof. Stephen Chan, Professor of the Department of Clinical Oncology; and Prof. Zhou Jingying, Assistant Professor
Prof. Alfred Cheng Sze-lok explains that using the latest single-cell sequencing technology, the research team was able to discover new molecular pathways by which liver cancer cells circumvent the therapy-armed immune system. The team further developed roadblocks and successfully eliminated the cancer cells through combination immunotherapy.