Protein CD155 in melanoma cells make skin cancer harder to treat

Queensland scientists have discovered a clue as to why patients do not respond well to treatment for melanoma.

QUEENSLAND scientists have discovered high levels of a protein found in human melanoma cells could be the reason patients do not respond well to treatment.
The new research, by QIMR Berghofer, found high levels of the protein CD155 in melanoma cells made the skin cancer harder to treat with immunotherapy.

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Senior scientist and immunology department co-ordinator Professor Mark Smyth, who led the research, said the study highlighted the central importance of CD155 to the effectiveness of immunotherapy for patients with metastatic melanoma – which was something that has not been shown before in humans.

He said the tumour appears to use the CD155 molecule to escape being hunted down by immune cells – called T-cells – and also to resist being killed off by immunotherapy.
“This 155 protein acts to demechanise the T-cells in a way that they can’t recognise the tumour cells effectively,” he said.

Mr Smyth said reducing tumour CD155 in people with metastic melanoma may be a way to improve the effectiveness of immunotherapy for patients and save the lives of many more people.

He said that after years without any success with immunotherapy, further research has allowed them to discover what does and does not work well in patients.

QIMR Clive Berghofer Medical Research Institute in Brisbane

The researchers used new imaging technology to examine pre-treatment tumour samples collected from patients in Brisbane, Sydney and Italy, and correlated the levels of CD155 with the patients’ survival outcomes.

Contributing author and Royal Brisbane and Women’s Hospital Medical oncologist Dr Elizabeth Ahern said the study also found patients with higher levels of the protein had worse health outcomes.
“It’s the quantity of CD155 proteins that makes it so immune evasive. It appears the T-cells can’t kill the tumour because the CD155 proteins are unbalancing the T-cells and turning them off before they can do their job,” she said.

“Currently there are no therapeutics used for melanoma that target CD155, so we hope to explore that pathway.

“We now want to focus on designing new immunotherapies that target the CD155 proteins to get them off the tumour.”