Immune cell discovery sparks hope for bowel cancer patients

Researchers have made an important discovery that is set to improve outcomes for patients diagnosed with bowel cancer — the second leading cause of cancer deaths in Australia. Their work has been published in the journal Science Immunology.

There is an urgent need to discover more effective treatments and improve bowel cancer screening, particularly for early-onset bowel cancer (in those aged 25–49 years). Australians born from 1990 onwards have double the risk of developing bowel cancer compared with those born in 1950, and these younger bowel cancer patients often have poorer outcomes as they typically present with late-stage disease.

Immunotherapy is one of the most promising new treatments for cancer, which involves boosting the ability of immune cells to recognise and remove cancer cells; however, less than 10% of bowel cancer patients respond to current immunotherapies. A research team led by the Olivia Newton-John Cancer Research Institute has now discovered that an important group of immune cells in the large bowel — gamma delta T cells — are crucial to preventing bowel cancer.

“Gamma delta T cells act as our frontline defenders in the bowel,” said Dr Lisa Mielke, principal investigator on the new study. “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 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.

“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 Marina Yakou, a PhD candidate at the Olivia Newton-John Cancer Research Institute. “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 preclinical models, this fundamentally changed the behaviour of these immune cells and we saw a remarkable reduction in the size of bowel cancer tumours.

“Our world-first research breakthrough paves a new roadmap for developing targeted combination immunotherapies to more effectively treat bowel cancer patients.”

This 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 is promising news for the 15,000+ Australians who are diagnosed with bowel cancer every year, over 1700 of whom are under 50 years of age.

“I’m hopeful that this new research may lead to more targeted immunotherapies that will result in less side effects, and hopefully even one day help to design better screening so people can be more accurately diagnosed and treated earlier,” said bowel cancer survivor Elise Stapleton.

Image caption: Representative fluorescent multiplex immunohistochemistry staining of healthy human colon, stained for T cells CD3 (yellow), CD8 (light blue), TCRδ (οrange), TCF-1 (green), epithelial cells (Pan-Cytokeratin,  red) and DAPI (dark blue).