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08 Jan 2021

On the frontline of immune protection

A type of immune cell lurks in tissues ready to jump into action to offer protection from infection.

Most immune cells migrate throughout the body via the blood. But a subset of T cells, coined tissue-resident memory T cells (Trm cells) by University of Melbourne Professors Francis Carbone and Thomas Gebhardt in 2009, were found to do what their name suggests.

These cells reside in tissues such as the skin, liver, lungs or gut, ready to fight infection at the site. Most importantly, their long-term persistence in tissues was shown to be key for swift and efficient protection.

“Essentially, our bodies deposit the ‘police’ to the areas where there’s always going to be trouble,” explains Professor Gebhardt.

“If you relied on circulating cells in the blood to control disease at sites where they’re needed, they would arrive too late, or potentially would never find the problem area.”

Over ten years, the last five at the Doherty Institute, researchers have been studying the role of Trm cells, with the ultimate goal of harnessing them to create better vaccines and immunotherapies for cancer.

University of Melbourne Professor Laura Mackay and her collaborators have made a series of discoveries to help unravel the function of Trm cells.

Professor Mackay uncovered the genes responsible for keeping the Trm cells in the tissues at the site of infection.

This work was published in seminal studies in 2013 and in 2016, together with Professor Gebhardt and University of Melbourne Professor Axel Kallies.

Professor Mackay then demonstrated that Trm cells in the skin can proliferate and remain there to fight infection by adding new populations of cells as required. This work was in collaboration with University of Melbourne Professor Scott Mueller.

Most recently, University of Melbourne PhD student, Simone Park, discovered how Trm cells control melanoma on the skin in a mouse model.

The research was performed in the laboratories of Professors Gebhardt and Mackay and showed the Trm cells were able to control tumours in the mice for the lifetime of the animal, which would equate to decades of protection in humans.

“Trm cells are hugely important, but we’re still at the stage of translating what we know from the basic biology,” says Professor Gebhardt.

This article was first published in the Celebrating Five Years of the Doherty Institute Impact Report.

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