‘Tiny first responders’ use powers for good against skin cancer

Researchers investigating a group of microscopic cells have discovered they can put the brakes on the rapid development of melanoma lesions.

Photograph of Cyril Seillet outside WEHI

Dr Cyril Seillet

A team at WEHI, in collaboration with the University of Queensland and the Peter MacCallum Cancer Centre have taken a close look at the relatively recently identified Group 2 innate lymphoid cells (ILC2) which are crucial for initiating and orchestrating immune responses.

UQ Diamantina Institute’s Professor Gabrielle Belz said their aim was to understand more about the function of these relatively recently identified cells, and their roles in melanoma.

“We wanted to investigate how ILC2 contribute to melanoma formation, because we already knew these cells harboured functions that could either suppress or stimulate production of cancerous tumours,” Professor Belz said.

“Previously, we understood very little about the underlying mechanisms of these intriguing cells, and whether they could be clinically relevant or targeted to apply the brakes on melanoma development.

“We discovered these cells can halt the rapid development of full-blown melanoma lesions and can potentially be harnessed to drive protective functions with potential immunotherapy applications.”

At a glance

  • Researchers have found that the recently identified Group 2 innate lymphoid cells (ILC2) can stop the development of melanoma
  • The discovery indicates potential for ILC2s to inform new immunotherapy strategies

Potential anti-cancer applications

Approximately two thirds of Australians will be diagnosed with a form of skin cancer before they are 70 years of age, and Australia and New Zealand have the highest rates of melanoma in the world.

WEHI’s Dr Cyril Seillet the research found that high ILC2 infiltration in human melanoma was associated with a good clinical prognosis.

“We found that ILC2 within tumours express the immune checkpoint inhibitor PD-1. We could enhance the anti-tumour activity of ILC2 with an existing cancer immunotherapy that blocks PD-1 interactions,” he said.

“ILC2s are also critical producers of a colony-stimulating factor known as GM-CSF, which coordinates the recruitment and activation of a type of disease-fighting white blood cell called eosinophils.”

“Our results identified not only that ILC2s have a critical function in melanoma immunity, but also that there was a potentially coordinated approach to harness ILC2 function for anti-tumour immunotherapies.

“Science underpins healthcare, and this opens a new pathway to explore targets not previously used as part of the immunotherapy regime, to both prevent development of metastasis and prevent resistance to therapy.”

Dr Nicolas Jacquelot, who helped lead the study at WEHI and is now at the Princess Margaret Cancer Centre in Canada, said the findings were promising.

“This shows our capacity to further increase immune responses against melanoma and the possibility to develop new immunotherapy strategies to boost the ILC2-eosinophil axis to fight tumour cells,” Dr Jacquelot said.

“This gives us real hope for improving outcomes for patients.”

Associate Professor Paul Neeson said the team at Peter Mac and the collaborative Centre for Cancer Immunotherapy was able to clinically validate the findings in human skin and, in particular, cases of melanoma.

“Our team showed these rare immune cells (ILC2) were present in human melanoma samples – both when patients were first diagnosed, and in patients with advanced disease,” Dr Neeson said.

This work was made possible with support from the National Health and Medical Research Council and the Victorian Government.

WEHI authors

Nicolas Jacquelot, Cyril Seillet, Yang Liao, Soroor Hediyeh-zadeh, Cynthia Louis, Qiutong Huang, Carolyn A. de Graaf, Mary Camilleri, Kylie Luong, Shengbo Zhang, Michael Chopin, Stephen L. Nutt, Joanna R. Groom, Daniel H. D. Gray, Ian P. Wicks, Melissa J. Davis, Wei Shi and Gabrielle T. Belz

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