Immunotherapies have led to major improvements in the survival of lung cancer patients. Yet today, only one in four lung cancer patients survive beyond 5 years, making lung cancer the biggest cause of cancer deaths globally.
Cancer cells develop mechanisms to evade immune attacks including downregulating antigen presentation. Concurrently, cancer cells hijack immune cells to orchestrate a tumour-supportive microenvironment, facilitating tumour progression and resistance to therapy.
This project will investigate the mechanisms by which cancer cell silence antigen presentation and neoantigen processing. We have identified a master regulator of this process and aim to fully characterise its mechanism of action. This knowledge will be used to design a small molecule inhibitor screen to identify drugs that could increase antigen presentation by tumour cells.
Experimental approaches will combine CRISPR/Cas9 knockout studies, in vitro biochemistry assays, in vivo studies, molecular biology including chromatin immunoprecipitation, RNAseq in preclinical models of lung cancer and in clinical samples.
