Higher Degree by Research Application Portal

Project Title 

Immunotherapy, particularly immune checkpoint blockade (ICB), has transformed the treatment of advanced lung cancer and mesothelioma. However, up to 70% of patients do not respond to these therapies, highlighting an urgent need to improve their effectiveness. 

One of the major barriers to successful immunotherapy is the presence of regulatory T cells (Tregs) in the tumour. These cells suppress the immune system and prevent it from attacking the cancer. Recent research suggests that Tregs inside tumours rely heavily on cholesterol and lipid metabolism to maintain their function. Interestingly, clinical studies have shown that patients taking cholesterol-lowering drugs may respond better to ICB, suggesting a potential way to target Tregs and improve outcomes. 

Project Overview 

This project aims to understand how altering lipid metabolism, particularly cholesterol, can reduce Treg-mediated immune suppression and enhance the body’s immune response to cancer. 

Aims  

• Investigate how cholesterol-lowering drugs affect Treg survival, function, and gene expression. 
• Assess how changes in lipid metabolism alter Treg suppression of anti-tumour T cells. 
• Use co-culture assays to test how modifying Treg metabolism impacts immune cell killing of cancer cells. 
• Apply CRISPR-Cas9 to disrupt key metabolic genes in Tregs and explore effects on immune suppression. 
• Evaluate how cholesterol-lowering treatments such as statins influence Treg populations in the tumour microenvironment. 
• Test whether combining metabolic therapies with ICB improves tumour control in mouse models of lung cancer and mesothelioma. 
• Analyse patient data to explore links between cholesterol metabolism genes, Treg signatures, and immunotherapy outcomes. 

Why Join This Project? 

• Work at the intersection of immunology, metabolism, and cancer therapy.
• Gain experience in cutting-edge techniques including CRISPR, flow cytometry, and in vivo tumour models, lipidomics and genomics.
• Contribute to translational research with real clinical relevance.
• Opportunity to collaborate with national experts in tumour immunology and lipid metabolism.

Multiple funding sources from Cancer Council WA, WA Department of Health.

Dr Jonathan Chee

jonathan.chee@uwa.edu.au, Institute for Respiratory Health

Kofi Stevens

Kofi.stevens@uwa.edu.au, Institute for Respiratory Health