Discovery by Croucher Scholar at HKUMed may improve liver cancer treatment

24 January 2022

Liver cancer (hepatocellular carcinoma, HCC) is the fifth most common cancer in Hong Kong and the third leading cause of cancer deaths, with more than 1,800 newly registered cases annually, underlining the importance of research that helps fight the disease.

Researchers led by Prof Irene Ng Oi Lin (Croucher Senior Medical Research Fellowship 2005 and 2013), Chair Professor of the Department of Pathology of the LKS Faculty of Medicine of The University of Hong Kong (HKUMed), have made important discoveries that could improve treatment of liver cancer.

Immune checkpoints are the normal part of the immune system to prevent an immune response from being too strong that it attacks healthy cells in our body. In cancers, the tumour cells hijack this mechanism. They bind with corresponding partner proteins on the surface of T cells, and send an “off” signal to the T cells to allow tumour cells evade immune surveillance. Immune checkpoint inhibitors can block the checkpoints, and help restore the immune attack on tumour cells, and their application in treating cancers was awarded the 2018 Nobel Prize in Physiology or Medicine.

Identifying immune checkpoints is important as immune checkpoint inhibitors are new and effective immunotherapy against cancers including liver cancer. However, while existing immune checkpoint inhibitors have partial effect in treating liver cancer, the response is still far from satisfactory. To improve the efficacy, it is essential to study the interaction between tumour cells and immune cells in the tumour microenvironment throughout the cancer progression.

The research team uncovered the important roles played by tumour-associated macrophages and identified an important TIGIT-NECTIN2 immune checkpoint axis (interacting partners) in liver cancer, which helps to create an immunosuppressive microenvironment in promoting the growth of liver cancer. This also indicates the possibility to restore the immune attack on tumour cells by inactivating the immune checkpoint.

As this could not be fully studied using traditional research strategies, the HKUMed research team used cutting-edge single-cell RNA sequencing technology to perform molecular profiling at unprecedented resolution on HBV-associated liver cancer, aiming to unmask the elusive mystery behind the immune checkpoint landscape in HBV-associated liver cancer.

“Our findings of the identification of the significance of TIGIT-NECTIN2 immune checkpoint axis in liver cancer provide important mechanistic insight for the design of newer generation of immune-oncology treatments,” said Prof Ng Oi-lin, who initiated the study. “More importantly, since the intrinsic difference between patients is large, patient stratification, ideally by using specific molecular biomarkers e.g. TIGIT-NECTIN2 immune checkpoint axis, is pivotal to identify the most susceptible subset of liver cancer patients for relevant precision treatment. This will likely demonstrate remarkable contrast, as compared to the conventional chemotherapy which operates in a one-size-fits-all manner and is proven ineffective in liver cancer.”

Their novel and translational findings provide useful pre-clinical foundation and mechanistic insight for developing onco-immunotherapeutics in precision liver cancer treatment. The findings were published in Nature Communications.

Prof Irene Ng Oi Lin is Loke Yew Professor in Pathology, Chair Professor and Head of Department of Pathology at The University of Hong Kong. She is also the Director of the State Key Laboratory for Liver Research at The University of Hong Kong. Her lab aims to unravel the molecular and cellular mechanisms of liver cancer with a current focus on the integrated functional genomics of liver cancer using genome-scale technologies coupled with clinical translational studies. Prof Ng received a Croucher Senior Medical Research Fellowship in 2005 and 2013.

To view Prof Ng’s Croucher profile, please click here.