New research has shed light on why advanced melanoma that has spread to the liver is particularly resistant to immunotherapy. Importantly, these new findings may help researchers find novel drug targets to extend the life of patients with liver metastases.

Melanoma Institute Australia and The University of Sydney PhD student Jordan Conway presented his findings virtually at the prestigious American Association for Cancer Research (AACR) Annual Meeting which began on the weekend. Jordan’s ground-breaking work is supported by the Emma Betts PhD Scholarship, in memory of 25-year-old Emma who passed away from melanoma four years ago.

“In patients with advanced melanoma, some metastases are more responsive to treatment than others, depending on the location in the body,” explained Jordan. “It was known that liver metastases are particularly unresponsive to immunotherapy, but we don’t yet fully understand why.

“By comparing the local immune environments within the different sites of melanoma metastases, we found different characteristics that may explain why liver metastases are notoriously resistant to immunotherapy,” Jordan added.

The body’s immune system is driven by T-cells. In the environment of liver metastases, the density of T-cells in this area is significantly less than in other locations, making the immune system much less effective and unable to fight invaders, such as tumours. Immunotherapy works by switching on the body’s own immune system, and it needs abundant, closely spaced T-cells to be effective.

This finding helps to explain why advanced melanoma patients with liver metastases do not respond as well to immunotherapy when compared to patients with metastases in other locations. The lower density of these T-cells could be driving the poor prognosis of melanoma patients with liver metastases.

The researchers also found that liver metastases also have a higher expression of a biomarker called TIM-3 in the liver. This may provide a therapeutic opportunity to improve outcomes for patients with liver metastases by using a different immunotherapy drug – one that specifically targets TIM-3.

Researchers will use this newfound knowledge about liver metastases to try to find novel drug treatments to extend, and ultimately save, the lives of patients whose melanoma has spread to the liver.
See Jordan’s conference poster here (ADD LINK)