Poster Presentation Australasian Melanoma Conference 2018

A novel murine model to study lymph node metastases (#110)

Katharina Hochheiser 1 2 , Simone L Park 1 , Thomas Gebhardt 1 , David Gyorki 2
  1. Department for Microbiology and Immunology, University of Melbourne, Melbourne, VIC, Australia
  2. Peter MacCallum Cancer Centre, Melbourne, VIC, Australia

Cutaneous melanoma is one of the most common cancers in people with fair skin, with Australia and New Zealand having the highest incidence in the world. While melanoma is often diagnosed at an early stage, with the potential for curative-intent surgery to the primary site, in some patients spread of tumour cells to the draining lymph nodes (sentinel lymph nodes, SLN) will have already occurred at the time of diagnosis. 


Patients harbouring micro-metastases in their SLNs have a 2.4 times higher risk of melanoma-specific mortality compared to patients without nodal involvement. However, most patients with SLN metastases will not relapse after surgical resection of these lymph nodes, which may indicate immune-mediated tumour cell control. In order to better understand the mechanisms underlying metastasis development and control, we have developed a transplantable tumour model of skin-contained cancer development by targeting melanoma cells to the outermost layers of mouse skin. This inoculation resulted in tumour formation with variable growth kinetics and penetrance. Early progressive tumour development often coincided with establishment of metastasis in skin-draining lymph nodes. Macroscopic metastases were detectable in wildtype mice. However, metastasis development and growth were particularly pronounced in mice genetically deficient for Perforin or Tumour Necrosis Factor alfa (TNFa), indicating a role for these soluble mediators in metastasis control.


Our novel epicutaneous melanoma model sets the stage for investigating the molecular mechanisms and identifying critical mediators in metastasis control, with the ultimate goal of refining SLN assessment and preventing immune escape in the clinic.