This project is flexible for Honours students, Masters students or Medical/clinical students.
Head and neck squamous cell cancer (HNSCC) is the eighth most common cancer diagnosed in Australia, with over 1000 deaths from advanced disease each year. For survivors, toxicity related to treatment of primary and nodal spread in the mouth and/or neck (surgery, radiotherapy, chemotherapy) can be morbid and protracted. There is accumulating evidence indicating the immunomodulatory effects of HNSCC by which it can escape and/or suppress the immune system, however much is still unknown about the different mechanisms of Immune suppression in HNSCC.
We have an ongoing clinical trial of HNSCC in which we obtain tumour samples that enable “multi-omic” analysis of the immune microenvironment of HNSCC and functional testing of novel bi-functional antibodies. The Flow Cytometry facility at QIMR Berghofer enables a very broad analysis of different immune cells present in HNSCC tumours, which can ultimately be related to the patient’s prognosis. Candidate cell-types that may contribute to HNSCC immune evasion include certain dendritic cells and myeloid-derived suppressor cells (MDSC). Different ligands expressed by HNSCC tumours may stimulate dendritic cells or MDSC, leading to immunosuppressive effects by reducing T-cell function. For functional drug testing of novel bifunctional antibodies, we are particularly interested in antibodies, which block multiple different tumour ligands simultaneously and therefore reduce immunosuppressive effects.
In the proposed project, the student will learn: 1) high-content flow cytometry of each of the relevant immune cells present in HNSCC; 2) In vitro techniques demonstrating immune-suppressive effects of HNSCC co-cultured with dendritic cells, MDSC, T-cells; 3) In vitro drug testing, using novel bi-functional antibodies.