In a medical first, scientists have hindered the growth of bowel cancers in mice by harnessing immune cells in the large intestine.
"We have discovered that an important group of immune cells in the large bowel – gamma delta T cells – are crucial to preventing bowel cancer," says immunologist Lisa Mielke from the Olivia Newton-John Cancer Research Institute at La Trobe University in Australia.
About 1 in every 10 cancer cases is bowel cancer. The second highest cause of cancer-related death worldwide, a lack of symptoms early in the disease's progression means it's often diagnosed too late to be treated.
"Our world-first research breakthrough paves a new roadmap for developing targeted combination immunotherapies to more effectively treat bowel cancer patients," says one of the study's lead authors Marina Yakou, a PhD student at the Olivia Newton-John Cancer Research Institute.
Yakou, Mielke, and a team of researchers from Australia and the US looked at tissue samples from bowel cancer tumors as well as samples from patients without bowel cancer.
They noticed a correlation between gamma delta T cells and favorable clinical outcomes in bowel cancer. When more of this type of immune cell was found in the tumors of bowel cancer patients, they were more likely to survive, and to experience more positive recoveries.
"Gamma delta T cells act as our frontline defenders in the bowel," Mielke says. "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."
Trillions of microorganisms make up the microbiome that resides in this section of the digestive tract. A healthy immune system relies on a wide variety of bacteria in the microbiome, though some are linked to disease.
Each region in the gut has its own function, and varies in the type and number of microorganisms present. The researchers wondered whether microbiome composition might influence the gamma delta T cells and other immune cells in the gut.
Analysis of cells from the gut of both humans and mice found molecular features in the large bowel that affect the ability of the gamma delta T cells to do their protective work. Whereas in the small intestine, those T cells were just getting on with their job.
"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," explains Yakou.
"This molecule (TCF-1) suppresses our natural immune response, the gamma delta T cells, from fighting off bowel cancer."
Perhaps most importantly, mice that had this TCF-1 protein deleted developed a heightened immune response against bowel cancer.
"This fundamentally changed the behavior of these immune cells and we saw a remarkable reduction in the size of bowel cancer tumors," Yakou says.
That means there's potential to manipulate the microbiome – and subsequently these T cells – in the large bowel in humans to improve their cancer-fighting abilities.
The team says this is a major advancement in our knowledge of the microbial and immune cell communities of the gut, and it could lead to earlier screening and therapies – for other cancers and other diseases too.
"Given the increasing incidence of bowel cancer in younger populations today, we're really interested in now dissecting out the exact relationship between the immune cells, the microbes, and the cancer cells within the gut," says Mielke.
"This new knowledge will help us understand and identify new risk factors that are important for the development of cancer, but also improve bowel cancer screening in the future."
The study has been published in Science Immunology.