A study links obesity with dampened immune detection of oral cancers in mouse models
10:42 AM
Author |
![red cells mouth opening dark background](/sites/default/files/styles/article_main_image/public/2023-04/mouth-teeth-tongue-cancer-cells.jpg?h=f0fb51a5&itok=Vizs6yQC)
A team from the University of Michigan Rogel Cancer Center and School of Dentistry, led by Yu Leo Lei, D.D.S., Ph.D., have identified a mechanism in mice for how obesity affects some oral cancers’ ability to escape from the immune system.
This study, published in Cell Reports, 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 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,” explained Lei. This feature drove the loss of immune subsets that were crucial for anti-tumor immunity in the tumor microenvironment.
The 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.
Lei says this is the first study establishing a mechanistic link between obesity with oral cancer immune escape. “We’re excited about the translational implications,” he continued.
Obesity is a common comorbidity in cancer patients. Two recent studies found that oral cancer patients who were on statins—medicines that lower cholesterol—showed improved overall and cancer-specific survival.
“This study establishes a mechanistic link for those observations and highlights the potential of targeting fatty acids metabolism in remodeling the host anti-tumor immune response,” said Lei.
Next, Lei’s team will explore how obesity regulates other immune-activating pathways and identify novel intervention targets for better oral cancer prevention in high-risk individuals.
More work needs to be done before this can move to the clinic.
Additional authors: Blake Heath, Ph.D., Wang Gong, research Investigator at the School of Dentistry, and Hülya Taner, D.D.S.-Ph.D. candidate.
Shared resources used: Flow – Flow Cytometry; Histology – Tissue and Molecular Pathology
Funding: Biden Cancer Moonshot Initiative (U01 DE029255), R01 DE026728, R01 DE030691, R01 DE031951, F31 DE028740, and T32 AI007413.
Paper cited: “Saturated fatty acids dampen the immunogenicity of cancer by suppressing STING,” Cell Reports. DOI: 10.1016/j.celrep.2023.112303
![Health Lab word mark overlaying blue cells](/sites/default/files/styles/article_sidebar/public/2022-12/health_lab_article_tag.jpg?h=d1cb525d&itok=fHtGF34e)
Explore a variety of health care news & stories by visiting the Health Lab home page for more articles.
![](/sites/default/files/2022-10/u-hospital-spring_large_1130x635.jpg)
Department of Communication at Michigan Medicine
Want top health & research news weekly? Sign up for Health Lab’s newsletters today!
![bottle cap red](https://www.michiganmedicine.org/sites/default/files/styles/card/public/2024-07/aluminum-bottle-cap-soda-lid.jpg?h=f0fb51a5&itok=dFOUDjX_)
![iv chemo bags](https://www.michiganmedicine.org/sites/default/files/styles/card/public/2024-07/chemotherapy-drugs-iv-bag-pole.jpg?h=f0fb51a5&itok=BTEQSIVp)
![white coats hanging and one swinging off hanger with purple haze over them and sunshine peeking through](https://www.michiganmedicine.org/sites/default/files/styles/card/public/2024-07/lab-coat-closet-doctor-closet.gif?h=d1cb525d&itok=tUUeek2w)
![close up photo of yellow pills lined up on a bright blue matt](https://www.michiganmedicine.org/sites/default/files/styles/card/public/2024-07/yellow-pills-rows-blue-background_0.jpg?h=f0fb51a5&itok=q-coTU_Z)
![two women, one older one younger, looking concerned listening to a provider across from them with back to camera](https://www.michiganmedicine.org/sites/default/files/styles/card/public/2024-07/older-woman-younger-woman-talk-with-counselor.jpg?h=f0fb51a5&itok=EO9CsfyP)
![rat in blue with yellow bright brain with blue abstract background](https://www.michiganmedicine.org/sites/default/files/styles/card/public/2024-07/rat_blue_bright_brain_yellow.jpg?h=ade979fe&itok=QAUYwnTy)