A team from the University of Michigan Rogel Cancer Center and School of Dentistry, led by Yu Leo Lei, DDS, PhD, 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 tumour microenvironment that promotes tumour 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 tumours, 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-tumour immunity in the tumour 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 remodelling the host anti-tumour 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.

Article: Saturated fatty acids dampen the immunogenicity of cancer by suppressing STING

Source: Michigan Medicine - University of Michigan