Characterisation of Merkel cell carcinoma links interferon response and neuroendocrine differentiation to patient survival outcome

ALEX CANEBORG 
Research Assistant
Rare Disease Oncogenomics
University of Melbourne Centre for Cancer Research

Merkel Cell Carcinoma (MCC) is a rare neuroendocrine cancer of the skin, with two distinct aetiologies – Merkel cell polyoma virus associated (VP) and UV sunlight associated (VN). Both MCC subtypes are highly immunogenic and exhibit good response current immune checkpoint immunotherapies (ICIs), with an overall objective response rate of ~50%. However, biomarkers predictive of ICI response are currently unknown and the mechanisms of acquired resistance are poorly understood. By characterising four new MCC cell lines (3 VN-MCC, 1 VP-MCC), we discovered two different transcriptional profiles in response to the interferon gamma (IFNg) – an important mediator of tumour inflammation with both pro and anti-tumor functions . These IFNg response signatures appeared to correlate with neuroendocrine and mesenchymal features of the respective cell lines. Importantly, both IFNg response and cellular differentiation profiles could be quantified in MCC tumours and had independent prognostic significance in a larger patient cohort.

Alex Caneborg completed his undergraduate and post-graduate degrees at the University of Edinburgh and Glasgow, completing his studies in 2016. After a brief internship at the NCCS in Singapore, working on tumour differentiation in Hepatocellular Carcinoma, he started work at the RADIO Lab in 2019. His work has been primarily focused on Merkel Cell Carcinoma, with a keen interest in the immune landscape of these tumours and identifying predictive features for immunotherapy response.