According to the American Cancer Society, approximately 150,000 new cases of rectal and colon cancer are diagnosed each year. While the numbers are slowly declining due to an increase in age-related screening, it remains the third most common cancer in the United States, affecting approximately one in 23 men and 26 women.
This cancer is also difficult to treat, with only 10% of patients responding to current immunotherapies. This means that treatment is usually surgery to remove all cancerous tissue. Therefore, although surgery can improve survival rates, it has a huge impact on the patient's quality of life.
Now, researchers at Australia's Olivia Newton-John Cancer Institute at La Trobe University have discovered that a patient's response to cancer depends on the effectiveness of a group of immune cells in the large intestine.
"Gamma-delta T cells are the frontline defenders in our gut," said lead researcher Dr. Lisa Milk, director of the Mucosal Immunity and Cancer Laboratory at the Olivia Newton-John Cancer Institute. "What's remarkable about these immune cells is that they constantly patrol and protect the epithelial cells lining the gut, 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 tumor, these patients reportedly had better treatment outcomes and higher survival rates."
However, this is only half the story. By looking at the entire microbiome in the large intestine, the researchers also found much higher concentrations of the molecule transcription factor 1 (TCF-1) on gamma-delta T cells. T cell-specific TCF-1 is also a core regulator of T cell development and function.
"We found that the abundance and diversity of the large intestinal microbiota results in higher concentrations of a molecule called TCF-1 on gamma-delta T cells compared to other areas of the gut," said Marina Yakou, lead co-author of the study. "This molecule inhibits our natural immune response - gamma delta T cells - against bowel cancer. When we used preclinical models to delete TCF-1 in gamma delta T cells, this fundamentally changed the behavior of these immune cells and we saw a significant reduction in the size of bowel cancer tumors. Our first-in-the-world research breakthrough paves the way for the development of targeted combination immunotherapies to treat bowel cancer patients more effectively."
This research is an exciting step forward in understanding the complex microbiome and how immune cells and the gut work together, with huge potential for new cancer screenings and better treatments that could both improve bowel cancer risk and improve treatment effectiveness.
The research was published in the journal Science Immunology.
For more on this discovery, the scientists present their findings in the video below.