According to the American Cancer Society, around 150,000 new cases of rectal and colon cancer are diagnosed each year. And while the number is slowly trending downward, thanks to an increase in pre-emptive age-related screening, it’s still the third biggest cancer in the US, affecting around one in 23 men and one in 26 women.
It’s also difficult to treat, with just 10% of patients responding to current immunotherapies. This means that treatment is more often than not surgery, removing all the cancerous tissue. As such, while it might improve survival rate, it can have a huge impact on quality of life outcomes for patients.
Now, researchers at the Olivia Newton-John Cancer Research Institute at La Trobe University in Australia have found that how a patient responds to cancer comes down to how effective a group of immune cells in the large bowel are.
"Gamma delta T cells act as our frontline defenders in the bowel,” said lead researcher Dr Lisa Mielke, Head of the Mucosal Immunity and Cancer Laboratory at the Olivia Newton-John Cancer Research Institute. “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.
"When we analyzed bowel cancer patient samples, we found that when more gamma delta T cells were present in the tumors, these patients were reported to have better outcomes and improved survival."
However, this was only half of the story. Looking at the entire microbiome in the large bowel, the researchers also found a much higher concentration of the molecule transcription factor 1 (TCF-1) on gamma delta T cells. The T cell-specific TCF-1 is also a central regulator of T cell development and function.
“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,” said lead co-author of the study, Marina Yakou. “This molecule 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 behavior of these immune cells and we saw a remarkable reduction in the size of bowel cancer tumors," said Yakou. "Our world-first research breakthrough paves a new roadmap for developing targeted combination immunotherapies to more effectively treat bowel cancer patients.”
This research is an exciting step forward in understanding the complex microbiome and how immune cells and the bowel function together, with huge potential in new screenings for cancer and better treatment to improve both bowel cancer risks and therapeutic outcomes.
The study was published in the journal Science Immunology.
For more on the discovery, the scientists present their findings in the video below.
