Immunotherapy is one of the most promising new treatments for cancer, which involves boosting the ability of immune cells to recognize and remove cancer cells. However, less than 10% of bowel cancer patients respond to current immunotherapies.
A new study published in Science Immunology was led by researchers at the Olivia Newton-John Cancer Research Institute.
Principal Investigator and Head of the Mucosal Immunity and Cancer Laboratory at the Olivia Newton-John Cancer Research Institute, Dr Lisa Mielke, announced a research breakthrough in the treatment of bowel cancer, saying: “We have discovered that an important group of immune cells in the large bowel - gamma delta T cells - are crucial to preventing bowel cancer.”
Frontline defenders
“Gamma delta T cells act as our frontline defenders in the bowel. What makes these immune cells extraordinary is that they constantly patrol and safeguard the epithelial cells lining the bowel, acting as warriors against potential cancer threats,” said Dr Mielke.
“When we analysed bowel cancer patient samples, we found that when more gamma delta T cells were present in the tumours, these patients were reported to have better outcomes and improved survival.”
The large bowel contains trillions of bacteria, viruses and fungi, collectively known as the microbiome. While some bacteria are associated with disease, others are extremely important for the immune system.
Improving treatment
Lead co-author of this study, Marina Yakou, PhD candidate at the Olivia Newton-John Cancer Research Institute, described how this new research may lead to improved treatments for cancer patients in the future.
“We discovered that the amount, and diversity of, the microbiome in the large bowel resulted in a higher concentration of a molecule called TCF-1 on Gamma delta T cells compared to other areas of the gut. This molecule (TCF-1) suppresses our natural immune response, the gamma delta T cells, from fighting off bowel cancer.”
“When we deleted TCF-1 in gamma delta T cells using pre-clinical models, this fundamentally changed the behaviour of these immune cells and we saw a remarkable reduction in the size of bowel cancer tumours,” said Ms Yakou.
“Our world-first research breakthrough paves a new roadmap for developing targeted combination immunotherapies to more effectively treat bowel cancer patients.”
New strategies
This research discovery also opens up new possibilities for understanding how the microbiome and immune cells in the bowel interact, which could lead to the development of new strategies to lower bowel cancer risk and better screen for bowel cancer.
This research study was made possible with thanks to funding from the National Health and Medical Research Council (NHMRC), Victorian Government acting through the Victorian Cancer Agency, Priority Driven Young Investigator Grant from Cure Cancer Australia Foundation, and a career recovery grant from Veski.
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