Northwestern Medicine researchers have discovered a "two-faced" group of cells at work in human colon cancer, with opposing functions that can suppress or promote tumor growth. These cells are a subset of T-regulatory (Treg) cells, known to suppress immune responses in healthy individuals
In this previously unknown Treg subset, the presence of the protein RORγt has been shown to differentiate between cancer-protecting and cancer-promoting properties.
The Northwestern team, led by Khashayarsha Khazaie, research associate professor at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, recently reported their findings in the journal Science Translational Medicine.
"The subset of Tregs that expand in human colon cancer is different from the Tregs that abound in healthy individuals in their ability to suppress inflammation," said Khazaie. "Since their discovery, Tregs have been assumed to be harmful in cancer based on the knowledge that they suppress immunity. More recent clinical studies have challenged this notion. Our work shows that Tregs, by suppressing inflammation, are normally very protective in cancer; it is rather their switch to the expression of RORγt that is detrimental."
The Northwestern team's work builds on observations, which demonstrated that the transfer of Tregs from healthy mice to mice with colitis or colitis-induced cancer actually protected the mice from colitis and colitis-induced cancer.
After identifying the abnormal Treg subset in mice with hereditary colon cancer, Khazaie and lead author Nichole Blatner, research assistant professor at Lurie Cancer Center, worked with Mary Mulcahy, MD, associate professor of hematology and oncology, radiology, and organ transplantation, and David Bentrem, MD, Harold L. and Margaret N. Method Research Professor in Surgery, of Northwestern University Feinberg School of Medicine, to look for the same cells in colon cancer patients.
"To our delight, we found the same Treg alterations in cancer patients," said Khazaie.
Of cancers affecting both men and women, colorectal cancer (cancer of the colon and rectum) is the second leading cancer killer in the United States. In 2012, approximately 140,000 Americans were diagnosed with colon or rectal cancer, while more than 50,000 deaths occurred from either cancer, according to the Centers for Disease Control.
"The significance of our discovery became apparent when by inhibiting RORgt in Tregs we were able to protect mice against hereditary colon cancer," Khazaie said.
He notes that several ongoing clinical trials exist based on targeted elimination of all Tregs in cancer patients. However, the discovery of Treg diversity in cancer, and its central role in control of cancer inflammation, may lead to new approaches for therapeutics.
"Tregs are actually very useful in the fight against cancer," he says. "We can do better by targeting RORγt or other molecules that are responsible for the expansion of this Treg subset, instead of indiscriminately eliminating all Tregs. We are very excited about the therapeutic options that targeting specific subsets of Tregs could provide in human solid tumor cancers, and that is our next immediate goal."
Khazaie's team is moving forward with plans to test novel drugs that inhibit RORγt.
Northwestern University: http://www.northwestern.edu
This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.
Flu cases across the US can be accurately estimated using Wikipedia searches, and fluey tweets from Twitter users also give the game away
Workers who have a creative outlet outside the office are more likely to be creative problem solvers on the job, a study suggests. Oh, and they have more fun.
Scientists to grow a crop of camelina plants genetically modified to produce fish oils that could be used in health supplements Continue reading...
Kent Kiehl has been interviewing psychopaths for more than 20 years. More recently he's acquired a mobile MRI scanner and permission to scan the brains of New Mexico state prison inmates. He talked with WIRED about what's different in the brains of psychopaths and why he views psychopathy as a preventable mental disorder.
In Snakes, Sunrises, and Shakespeare, evolutionary psychology pioneer Gordon H. Orians traces the roots of today's human quirks in the minds of our ancestors
The World Health Organization says an outbreak of the deadly Ebola virus in West Africa has been linked to the deaths of more than 120 people. As of Monday, the organization recorded a total of 200 suspected or confirmed cases of Ebola, which is normally found in central or eastern Africa, in…
To see if low blood sugar sours even good relationships, scientists used an unusual tool: voodoo dolls representing spouses. As hunger levels rose, so did the number of pins.
A Beijing artist who collected a jar of air from Provence, France, sold it at auction "to question China's foul air and express dissatisfaction."
With purported activity against cardiac disease, cancer and even ageing, the pressure on resveratrol to deliver is enormous
Health workers responding to an Ebola outbreak in Guinea had no maps to go on, so they turned to the internet for help