Immune cell breakthrough could lead to new treatments

Updated. A research team from Federation University and the Murdoch Children's Research Institute (MCRI) has been awarded nearly $1 million for a three-year research project to develop their recently published findings about how an important type of immune cell develops in humans, potentially paving the way for a new generation of immune-based treatments.

The study is funded by the National Health and Medical Research Council (NHMRC) and will be led by Federation's Professor of Immunology Stuart Berzins and Associate Professor Dan Pellicci from the MCRI, who hope the study will build on their recent study published in the prestigious journal Science Immunology earlier this year that revealed how a specialised subset of unconventional white blood cells develops in humans.

"These cells are one of several types of white blood cells in your body. We know they're important for protection against different forms of cancer, infections and other illnesses, but our recent findings have shown how they develop and could potentially be targeted in new treatments," Professor Berzins said.

These so-called gamma-delta T cells are quite different from most other human immune cells. They respond to different stimuli, have distinct functions, and emerged early in our evolution.

Unlike most other immune cells, gamma-delta T cells are found across the spectrum of the animal kingdom, from humans all the way through to hagfish, lampreys and other primitive jawless vertebrates that emerged hundreds of millions of years ago.

"They coordinate the activities of different parts of the immune response, so it's not surprising that gamma-delta T cell defects are associated with the progression of a wide range of illnesses, including cancer and microbial infections," Professor Berzins said.

Because they can impact immunity to many different diseases and infections, gamma-delta T cells are seen as an attractive target for immune-based therapies, but a significant stumbling block has been the lack of knowledge about how they develop.

"Some people have defects of gamma-delta T cells where they don't have enough cells, or the cells don't work particularly well, but treating this requires that we first understand how they develop and work in the first place," Professor Berzins said.

The researchers unexpectedly found that the main subset of gamma-delta T cells are produced throughout our lives in the thymus organ. This countered previous scientific doctrine that they were only made during fetal development and raises the possibility that new treatments could target this process at any age.

Importantly, the study also discovered how gamma-delta cells develop, which means researchers can now investigate how defects occur and whether specific parts of the pathway can be targeted to treat or prevent illnesses.

"It was assumed that once you were born, development of these cells stopped, but we saw signs that maybe that assumption was wrong," Professor Berzins said.

"Our study has shown definitively that it was incorrect and that humans make these cells throughout our lives.

"This means that we can potentially intervene in that process, whereas if the previous dogma was correct, there would be little opportunity to intervene in a way that would improve your immunity.

"Now our group and other laboratories can build on that research."

The pioneering study was the result of a collaboration between Federation University's Professor Berzins and PhD student Louis Perriman and a group led by Associate Professor Dan Pellicci from the MCRI, which is the administrating institute. Co-collaborators included researchers at the Fiona Elsey Cancer Research Institute and Peter Doherty Institute of Infection and Immunity.

Professor Berzins and Associate Professor Pellicci have already presented their findings at several international conferences and scientific institutes.

Last week the project team was awarded a grant of $980k from the NHMRC to fund further research into unconventional T cells to support the development of new immune-based therapies.

Professor Berzins began looking at these types of cells earlier in his career, working with researchers at the University of Melbourne and the Peter MacCallum Cancer Centre. The researchers consistently found that unconventional T cells were defective in cancer patients.

The findings weren't direct evidence of their importance but were highly suggestive of it. That work led to more studies of these types of cells.

"We have recently been studying how unconventional T cells develop so that we understand what is required for the body to establish a functional immune system. That's an important element of the work we recently published and what we hope to achieve in this newly funded study," Professor Berzins said.

"The international recognition and funding this research is receiving is very gratifying. It confirms the importance of the discoveries we have made and shows that Federation University continues to produce world-leading research, including in the area of immunology, which is more traditionally associated with larger metropolitan universities and institutes."

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