Dr Florian Wiede
Monash University (2016-2017); The University of Melbourne (2018)
Bowel, Breast, Lung, Lymphoma and Melanoma
The immune system is a complex network of cells that allows the human body to battle infectious diseases, suppress autoimmune disorders or combat the development of cancer. Cytotoxic T cells, a subset of specialised immune cells, play a critical role in the killing of tumour cells. However, tumours develop complex inhibitory mechanisms that can ‘silence’ cytotoxic T cells, thereby allowing for tumor growth and dissemination. We have recently identified the protein PTPN2 as a key regulator of cytotoxic T cells and we could show that PTPN2 prevents cytotoxic T cells from killing tumour cells. We will explore whether the inhibition of PTPN2 might enhance the T cell’s ability to attack and kill tumour cells.
What is the need?
The inability of the immune system to initiate a robust anti-tumour response is often linked to poor prognosis for patients with solid tumours including advanced melanomas, breast, renal and ovarian cancers. In particular, tumours can express molecules such as PD-1 ligand and CTLA-4 that effectively ‘silence’ anti-tumour T cells. While therapies involving the administration of drugs to boost tumour-specific T cell responses have delivered promising results in the clinic, the ongoing search for novel targets to further improve cancer therapy is critical.
What is the impact of this research?
Our work will shed light into mechanisms that contribute to cytoxic T cell exhaustion and the non-responsiveness of the immune system to tumour cells. It will also help to further improve existing therapies using drugs that are directed against PD-1 ligand and CTLA-4. By targeting molecules that prevent a robust tumour specific T cell response, we will define a novel immunotherapy for a more effective cancer treatment.
Cancer Council Research Grant