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Study finds link between obesity with oral cancer immune escape

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Michigan | May 17, 2023 9:08:16 AM IST
A mechanism for how obesity impacts the capacity of some oral malignancies to bypass the immune system has been uncovered in a study.

A team from the University of Michigan Rogel Cancer Center and School of Dentistry, led by Yu Leo Lei, D.D.S., Ph.D. Obesity helps to produce a sort of tumour microenvironment that promotes tumour growth, according to this study published in Cell Reports. The link between saturated fatty acids, the STING-type-I interferon pathway, and NLRC3 explains how this happens.

"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. (ANI)

 
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