Date: Friday, 12 November 2021

Venue: Seminar Room 2&3, G/F, Laboratory Block, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong

Time: 5:00 p.m. - 6:00 p.m.

5:00 p.m.

Speaker: Miss Qingmei ZHANG (MPhil candidate)
Primary Supervisor: Dr. Yick Pang CHING
Presentation Title: TAX1BP2 stimulates type I interferon secretion through the activation of the STING pathway
Abstract: Liver cancer (hepatocellular carcinoma, HCC) is one of the most common malignancies worldwide and the third leading cause of cancer death in Hong Kong. The prognosis of HCC patients is commonly poor because of the late detection. Recently, immunotherapy has gained attention for the treatment of cancer patients with advanced stage. However, little is known about how to prime the T cells against immunogenic tumours, which involves type I interferons (IFNs) production. The Stimulator of Interferon Genes (STING) adaptor protein, which is an important component of cellular DNA sensing machinery, activates innate immune responses through the production of type I IFNs. Emerging evidence has shown that centrosome abnormalities are universal among tumour cells, and can lead to immune escape. Interestingly, we found that the Tax1 Binding Protein 2 (TAX1BP2), a centrosomal protein and a putative tumour suppressor in HCC, upregulated STING at both protein and transcript levels in HCC cells. Activation of STING also triggered the activation of IRF3, which is a major modulator for type-I IFN response. Thus, we would like to further characterize the molecular mechanism by which TAX1BP2 mediates the innate immune responses via the STING signaling pathway.

5:30 p.m. 

Speaker: Mr. Yunong XIE (MPhil candidate)
Primary Supervisor: Dr. Carol Man TONG
Presentation Title: Targeting AXL signaling axis activates antitumor immunity in tyrosine kinase inhibitor (TKI)-resistant liver cancer
Abstract: Sequential therapy is the current standard of care for unresectable hepatocellular carcinoma (HCC). First-line targeted therapies using TKI and second-line immunotherapies are often administered sequentially when patients develop resistance to the first-line treatment. However, the response to immunotherapy following TKI treatment is often compromised in TKI-resistant HCC. In this study, we find that receptor tyrosine kinase AXL is upregulated in TKI-resistant HCC, which alleviates the mitochondrial oxidative stress and subsequent cytosolic mitochondrial DNA leakage, conveying an immune-evasive phenotype as demonstrated by an attenuated interferon signaling and immunogenic cell death response. Suppression of AXL in TKI-resistant HCC cells abrogate the protective effect and activate the immunogenic responses. Blockade of AXL with a selective inhibitor BGB324 reduces tumor burden and prolongs survival in a pre-clinical TKI-resistant HCC mouse model. These findings suggest that targeting AXL could activate the antitumor immunity, which might be a better treatment option for HCC patients who progress on TKI treatment.

ALL ARE WELCOME

Should you have any enquiries, please feel free to contact Miss Cynthia Cheung at 3917 9748.