Researchers awarded $5m NHMRC Synergy Grant to improve immunotherapy against melanoma

A Melbourne-based research team has received a five-year Synergy Grant from the National Health and Medical Research Council (NHMRC). The $5 million funding will be used to develop a new program of work exploring interactions between microbiota and T cells to enhance melanoma immunotherapy.

Synergy Grants are awarded for ‘for outstanding multi-disciplinary research teams to work together to answer complex questions’, and this collaborative project is being led by Professor Shahneen Sandhu, from The Sir Peter MacCallum Department of Oncology at the University of Melbourne, and Consultant Medical Oncologist and Research Lead for the Melanoma Medical Oncology Service at the Peter MacCallum Cancer Centre (Peter Mac). It also includes University of Melbourne’s Professor Sammy Bedoui and Dr Vanessa Marcelino, Professor Tony Papenfuss from WEHI, and Dr Lavina Spain and Professor Grant McArthur from Peter Mac.

Professor Jane Gunn AO, Dean of the Faculty of Medicine, Dentistry and Health Sciences, congratulated the team on their successful NHMRC grant, acknowledging the hard work that goes into each application.

“It’s inspiring to see researchers collaborating across the Doherty Institute, Peter Mac and WEHI. Ensuring a successful project across disciplines and organisations is both challenging and rewarding. It will be fantastic to see the innovative ways this team will improve treatments for cancer patients with melanoma, and the positive effects on our wider community,” Professor Gunn said.

Australia and New Zealand have the highest rates of melanoma in the world, resulting in over 1300 deaths each year. Cancer drugs called ‘combination immune checkpoint inhibitors’ (ICIs) have significantly reduced death from melanoma. However, approximately fifty per cent of patients will still die and many experience severe immune-related adverse events because of the treatment. The reason why some cancer patients respond well, and others don’t, is still unclear.

Preliminary data, generated by Professor Bedoui, Dr Marcelino and Professor Sandhu, from cell culture assays, mice and melanoma patients receiving ICI drugs, suggests that immune system T cells are influenced by substances made when the bacteria, found in our gut, break down food. These substances, otherwise known as microbiota-derived metabolites (MDMs) influence how the immune system responds to melanoma.

The team’s goal is to understand how these metabolites enhance how T cells respond to melanoma and assess their potential to improve immunotherapy in the clinic.

“We have assembled a team of immunologists, microbial ecologists, computational biologists, and melanoma clinicians with diverse expertise to address these questions using advanced integrative analyses in mouse models and prospective melanoma patient datasets,” said Professor Sandhu.

Dr Marcelino stated, "This field of research is still in its infancy, and we hope that new insights gained from our iterative, clinical, preclinical, and bioinformatic studies will translate into therapeutic interventions to improve patient outcomes.”