Director's Seminar Series - Professor Thomas Gebhardt, The University of Melbourne

Helper and killer T cell responses to cutaneous melanoma

Host: Anne Bruestle

Abstract

We have developed a transplantable melanoma model that approximates distinct disease stages seen in patients, including progressively growing tumors with metastatic spread, stably controlled tumors, as well as long-term persistence of occult melanoma cells in absence of macroscopic tumors. We have built key technologies around this model, including curative-intent surgery, in vivo imaging, as well as a gene editing to generate melanoma variants tailored to address defined experimental questions. Combined, these tools uniquely permit tracking, manipulation and imaging of melanoma and tumor-specific T cells, including a direct visualization of localized T cell-mediated tumor suppression. We are currently using this set-up to elucidate the contribution of tissue-resident T cells and other immune cells to the durable control of cutaneous melanoma and metastatic disease, and to uncover basic molecular pathways involved in efficient tumor suppression. Such knowledge has the potential to inform the development and refinement of future cancer immunotherapies.

Biography

Thomas is a laboratory head in the Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity.  He has a background in medicine and biomedical research and joined the University of Melbourne in 2005 as a postdoctoral fellow.  Over the years, Thomas has been supported by prestigious fellowships, including from the Sylvia & Charles Viertel Charitable Foundation, and currently holds a NHMRC Investigator followship. His team identified and coined ‘tissue-resident memory T cells’ (TRM) as the T-cell population that dominates immune protection at body surfaces. They also pioneered the functional and transcriptional characterisation of TRM cells and more recently described an important function of TRM cells in suppressing clinically occult melanoma. The overall goal of his team is to better understand the role of TRM cells in health and disease and to develop immunotherapies that these cells for improved clinical outcomes in infection, inflammation and cancer.