According to new research from the Australian National University (ANU), a protein in the immune system can be manipulated to help defeat the bowel cancerwhich claims more than 100 lives in Australia every week, but around 90% of cases can be treated successfully if detected early.
According to lead author Dr Abhimanu Pandey, from ANU, the protein, known as Ku70, can be activated or 'turned on' like a light switch using a combination of new and existing drugs.
There research was published in Science Advances.
Bowel cancer: this is how the Ku70 protein works
“In its activated state, the protein acts as a surveillance system, detecting signs of damaged DNA in our cells,” Dr Pandey said. DNA is the genetic code of life. Damaged DNA is a danger signal that can transform healthy cells into cancer cells.”
“Our research shows that Ku70 can 'cool down' tumor cells and absorb damaged DNA. The protein prevents cancer cells from becoming more aggressive and spreading throughout the body, essentially deactivating them and keeping them in a dormant state.”
Bowel cancer is the fourth most diagnosed cancer in Australia. It is estimated that one in 20 people will be diagnosed with bowel cancer by age 85. Under the National Bowel Cancer Screening Program, Australians aged 50 to 74 receive a free bowel screening test every two years, an effective measure to promote early diagnosis and treatment of bowel cancer.
While the risk of developing bowel cancer is higher in people over the age of 50, an increasing number of young Australians are being diagnosed with the disease. One in nine new cases of bowel cancer now occur among Australians under the age of 50.
Professor Si Ming Man, also from ANU, said future bowel cancer screening methods could include checking Ku70 levels in precancerous polyps, abnormal growths of tissue in the colon, before the cells healthy cells become cancerous.
“Our research shows that Ku70 is a good immune biomarker, meaning it helps us predict who will fare better or worse after being diagnosed with bowel cancer,” Professor Man said.
Ahead of World Cancer Day on February 4, ANU researchers are calling on people of all ages to be aware of the signs and symptoms of bowel cancer. “We know that early diagnosis and treatment are key to beating not just bowel cancer, but potentially other cancers too,” Professor Man said.
“We hope that the cancer research conducted at ANU will help raise awareness of cancer prevention, detection and treatment on this important day.”
Each year, more than 15,500 Australians are diagnosed with bowel cancer, making it the second leading cause of cancer death in the country. Over 1,700 (one in 10) of those diagnosed are young Australians under the age of 50 and this incidence is increasing.
There is an urgent need to discover more effective treatments and improve bowel cancer screening, particularly for early-onset bowel cancer (those between the ages of 25 and 49). Australians born in 1990 or later have double the risk of developing bowel cancer compared to those born in 1950. These younger patients with bowel cancer often have worse outcomes as they typically have advanced-stage disease.
Immunotherapy is one of the most promising new treatments for bowel cancer, as it involves boosting the ability of immune cells to recognize and eliminate cancer cells. However, fewer than 10% of bowel cancer patients respond to current immunotherapies.
The results of a study published October 6, 2023 in Science Immunology, were conducted 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, explained the importance of this research breakthrough.
“We found that an important group of immune cells in the large intestine, gamma delta T cells, are crucial for preventing bowel cancer.”
“Gamma delta T cells act as our first-line defenders in the gut. What makes these immune cells extraordinary is that they constantly patrol and safeguard the epithelial cells lining the intestine, acting as warriors against potential cancer threats,” said Dr. Mielke.
“When we analyzed samples from bowel cancer patients, we found that when more gamma delta T cells were present in the tumors, these patients had better outcomes and improved survival.”
The large intestine contains trillions of bacteria, viruses, and fungi, collectively known as the microbiome. While some bacteria are associated with disease, others are extremely important to the immune system.
Co-lead author of this study, Marina Yakou, Ph.D. candidate at the Olivia Newton-John Cancer Research Institute, described how this new research could lead to better treatments for cancer patients in the future.
“We found that the quantity and diversity of the microbiome in the large intestine results in a higher concentration of a molecule called TCF-1 on Gamma delta T cells compared to other areas of the intestine. This molecule (TCF-1) suppresses our natural immune response, gamma delta T cells, from fighting bowe
l cancer.”
“When we knocked out TCF-1 in gamma delta T cells using preclinical models, this dramatically changed the behavior of these immune cells, and we observed a dramatic reduction in the size of bowel cancer tumors,” Yakou said.
“Our first global research breakthrough opens a new roadmap for developing targeted combination immunotherapies to more effectively treat bowel cancer patients.”
This research finding also opens up new possibilities for understanding how the microbiome and immune cells interact in the gut, which could lead to the development of new strategies to reduce the risk of bowel cancer and improved screening for bowel cancer.
A mystery that has baffled bowel cancer researchers for decades has been solved by scientists at the Cancer Research UK Beatson Institute and the University of Glasgow.
Generations of doctors and researchers have struggled to understand why a bowel cancer patient's immune system ignores the cancer, rather than attacking it.
Now, the Glasgow team think they know how bowel cancer 'blinds' the immune system so that it cannot see the cancer and is therefore unable to destroy it.
The discovery, published in Cancer Immunology Research, opens the door to potentially reversing or preventing this process, which would allow the immune system to “see” intestinal cancer cells and prevent them from growing and multiplying.
Dr Seth Coffelt of the Cancer Research UK Beatson Institute and the University of Glasgow, who led the research, said: “Normally immune cells keep things as they should be, patrolling the gut like security guards, tackling any bacteria harmful and keeping the intestine healthy.
“When cells in the gut become cancerous however, they fire these “security guards” and all the methods these immune cells use to communicate with each other to coordinate an immune response are no longer produced.
“The cancer doesn't want the immune cells to recognize it as a threat, so they manipulate the immune cells so they can't see the threat and simply pass on, letting the cancer do its damage.”
Bowel cancer is the second most common cause of cancer death in the UK with around 16,800 deaths in the UK each year, or 46 per day. Around 4,000 people are diagnosed with bowel cancer in Scotland every year.
The research team focused on a particular type of immune cell called gamma delta T cells. Bowel cancer starts in the epithelial cells that line the intestine, and these T cells “patrol” this area attacking any threats, such as damaged cells or small tumors, before they can cause us harm.
Scientists already knew that when bowel cancer is present, immune cells capable of killing the cancer often fail to act against bowel cancer, but they didn't know why.
Using tissue samples from intestinal tumors donated by patients in Scotland and other countries, the team was able to identify the specific mechanism used by tumor cells to 'rewire' gamma delta T cells at a molecular level.
The team now hopes that further research may offer treatments that can reverse this 'rewiring'. Uncovering how cancer cells trick the immune system offers the potential for new treatments that could reactivate these crucial immune cells.
Dr Coffelt added: “Our discovery means that if we could find a way to artificially engage 'blind' T cells with a drug so that the T cells can 'see' the cancer again, we could find a new effective way to treat bowel cancer”.
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