Over 60% of the world’s VDCs occur in Asia, and Asians appear to be uniquely susceptible to three significant infection-related cancers: Hepatitis B-related Hepatocellular Carcinoma; Helicobacter Pylori (HP)-related gastric cancer, and Epstein-Barr virus (EBV)-related Nasopharyngeal Carcinoma (NPC).
The major aims of this theme are to:
The tumour microenvironment in different VDCs, including the stroma containing cancer-associated fibroblasts (CAFs) and endothelial cells, is hypothesised to play a critical role in generating heterogeneity in response to immune checkpoint inhibitors, likely by influencing gene expression in tumour cells and the associated immune milieu.
Specific aims are to:
It is hypothesised that VDCs manipulate their immune microenvironment to induce immunosuppression that prevents effective anti-cancer immunity and curtails responses to immunotherapy.
In this theme, the specific aims are to:
We hypothesise that VDCs display distinct changes in metabolism that generate unique metabolic microenvironments. Such changes influence and shape the phenotype of TILs to promote immunosuppression, tumour progression and/or resistance to immunotherapy.
Therefore, we aim to:
Theme 5 will focus on building the next generation of cutting edge antibody and cell-based immunotherapies that will leverage on the target discoveries of Themes 1-4, and rationally designing single and combination studies informed by this new knowledge, including a holistic integrated cancer immunogram for VDCs incorporating collective information from the characterisation of the VDC tumour microenvironment in Themes 1-4. A key consideration is to build therapeutic platforms and strategies that we can realistically compete in globally.
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