Impressions

Saturated Fatty Acids Promote Immune Escape of Oral Cancers

A team from the University of Michigan Rogel Cancer Center and School of Dentistry, led by Yu Leo Lei, DDS, PhD, has identified a mechanism in mice that explains how obesity affects some oral cancers’ ability to escape from the immune system.

The study, published in Cell Reports,¹ found that obesity helps to establish a type of tumor microenvironment that promotes tumor progression. How exactly this happens lies in the relationship between the saturated fatty acids, the STING-type-I interferon pathway, and NLRC3.

“We tend to think about the increased risks for gastrointestinal tumors, breast cancer, pancreatic cancer and ovarian cancer when it comes to obesity,” said Dr. Lei, a pathologist-immunologist and lead author of this study. “Multiple recent prospective cohorts involving millions of individuals from several continents revealed a previously underappreciated link between obesity and oral cancer risks.”

Myeloid cells in obese mice were insensitive to STING agonists and were more suppressive of T cell activation compared to the myeloid cells from leans hosts, Dr. Lee said. This feature drove the loss of immune subsets that were crucial for anti-tumor immunity in the tumor microenvironment.

The research team found that saturated fatty acids can block the STING pathway, which is induced by cytosolic DNA and promotes antigen-presenting cell maturation, by inducing a protein called NLRC3.

This is the first study establishing a mechanistic link between obesity and oral cancer immune escape, Dr. Lee said.

Dentures Could Harbor Pneumonia-Causing Bacteria

Researchers from Cardiff University in the UK found that dentures could play a role in causing the bacteria that leads to pneumonia, according to a study published in the Journal of Medical Microbiology.²

For the study, the research team began by taking mouth, tongue and denture swabs from a group of hospital patients who had pneumonia and wore dentures and compared the swabs to samples taken from denture-wearing patients in care homes who did not have pneumonia. The team then analyzed the samples to identify the abundance and types of microbes that were present. Researchers were looking for microbes that could cause pneumonia and whether there were any significant differences between the two groups.

“We were expecting to see a difference but were surprised to see 20 times the number of potentially pneumonia-causing bacteria on dentures in people with pneumonia, compared to people without.” said Josh Twigg, PhD, lead author of the study.

Dr. Twigg and his team speculate that the dentures could play a role in causing pneumonia. If the dentures are not cleaned properly, they could provide a new surface where disease-causing microbes can colonize. People who wear dentures may then be aspirating saliva containing harmful microbes into their lungs where an infection can then take hold.

However, while this study identifies a possible connection, Dr. Twigg said results did not conclude that people got pneumonia because they were wearing dentures. “It’s just showing that there is an association there,” he said. “This research is an early step in trying to unravel that puzzle of what exactly is the sequence of events.”

While more research needs to take place, the public can still learn from the findings.

“Our research has shown that there are potentially harmful microbial communities on dentures, so it is important to clean dentures thoroughly.”

Soft Gums More Prone to Inflammation

A group of scientists from Tohoku University have discovered that gingiva stiffness influences the properties of gingival fibroblasts – cells that contribute to the formation of connective tissue that anchor teeth to the gingiva – which in turn affects whether inflammation is likely to occur and make gingival fibers difficult to form. Their findings were published in the journal Scientific Reports.³

“We discovered that soft gingiva results in inflammation and hinders the development of gingival fibers,” said Masahiro Yamada, DDS, PhD, of Tohoku University’s Graduate School of Dentistry.

Many factors can lead to gingival recession, such as gum disease, over-brushing and chewing tobacco. But this is the first time gingival stiffness has been attributed to biological reactions. Although fibroblasts play an important role in the maintenance, repair and healing of the gingiva, they also produce various inflammatory and tissue-degrading biomolecules that degrade the gingival fibers. In addition, fibroblasts are associated with immune responses to pathogens.

For this study, the research team created an artificial culture environment that simulated soft or hard gingiva and cultured human gingival fibroblasts on them. They discovered that hard gingiva-simulated stiffness activated an intracellular anti-inflammatory system in the gingival fibroblasts that prevented inflammation. Yet, soft gingiva-simulated stiffness suppressed the fibroblastic anti-inflammatory system. This increased the likelihood of inflammation and resulted in less collagen synthesis.

“The results are expected to accelerate the development of advanced biomaterials to control local inflammation or microdevices that simulate the microenvironment of inflammatory conditions,” Dr. Yamada said.

Some Arthritis Flare-Ups May Be Rooted in Gum Disease

Patients with periodontal disease are less likely to respond to rheumatoid arthritis treatments, but new research may help explain this link between gum disease and an otherwise disparate condition. The findings, published in Science Translational Medicine,⁴ suggest that breaches in damaged gums allow bacteria in the mouth to seep into the bloodstream, activating an immune response that ultimately pivots to target the body’s own proteins and causes arthritis flare-ups.

“If oral bacteria are getting in and repeatedly triggering immune responses relevant to rheumatoid arthritis, that could make it harder to treat,” says Dana Orange, PhD, a professor of clinical investigation in the laboratory of Robert B. Darnell at The Rockefeller University. “When doctors encounter arthritis patients who do not respond to treatment, it would be worth it to make sure they aren’t missing an underlying gum disease, which is quite treatable.”

The Darnell lab followed a small group of arthritis patients over the course of several years, collecting weekly blood samples and looking for changes in gene expression to help explain why painful flare-ups occur. Researchers noticed a surprising trend. Two of their patients, who had moderate to severe periodontal disease, had repeated episodes of oral bacteria in their bloodstreams even when they weren’t having dental work.

Dr. Orange knew that rheumatoid arthritis patients generally have autoantibodies in their bloodstream (rheumatoid arthritis is an auto-immune disease, wherein antibodies attack the body’s own proteins and peptides). In many cases, autoantibodies take specific aim at proteins bearing the signs of citrullination, a process in which one amino acid in the protein is converted into a different one.

Upon further examination, the researchers discovered that the oral bacteria they detected in the blood are also citrullinated in the mouth, much like the proteins targeted by autoantibodies in arthritis. They then demonstrated that the same autoantibodies that take potshots at the body’s citrullinated proteins activate in response to citrullinated bacteria.

The results may explain why arthritis treatments do not work as well in patients with periodontal disease, according to the authors. If the gums are continuously releasing immune triggers into the bloodstream, treating arthritis without first solving the periodontal problem is like trying to haul water out of a ship without first plugging up its leaks.

“Gum disease is quite curable; rheumatoid arthritis can be much more difficult to treat,” Dr. Orange said. “Our results indicate that periodontal disease leads to leaky gums that allow oral bacteria to enter the blood repeatedly. This level of oral bacteria in blood doesn’t cause obvious symptoms, so the patients were not aware this was happening, but they do trigger inflammatory and auto-antibody responses that are highly relevant to rheumatoid arthritis.”

Study: Children of Racial and Ethnic Groups at Higher Risk of Tooth Decay

A cohort study led by Sung Eun Choi, SM, PhD, assistant professor at the Harvard School of Dental Medicine, found that compared to white youths, children and adolescents from all other racial and ethnic groups were at higher risk of tooth decay. The study was published in JAMA Network Open.⁵

Using electronic health records of 61,083 U.S. children from 2014 to 2020, researchers measured and analyzed racial and ethnic disparities in the risk of tooth decay. Elastic net regularization was used to select variables to be included in the model among medical conditions, dental procedure types and individual- and community-level socioeconomic factors.

The analysis found that compared with white children, all other racial and ethnic groups among those aged 0 to 5 years, Hispanic and Black children among those aged 6 to 10 years and Black adolescents among those aged 11 to 18 years were at a higher risk of tooth decay. Additionally, the research team discovered that large proportions of disparities in time to first tooth decay associated with race and ethnicity were explained by individual- and community-level factors, including insurance and types of dental procedures.

“These findings suggest that efforts to reduce racial and ethnic disparities in tooth decay should target different individual- and community-level factors, depending on age and racial and ethnic group,” the authors state.