Researchers from the University of Michigan Rogel Cancer Center and School of Dentistry have made a groundbreaking discovery that sheds new light on the relationship between obesity and oral cancer. Their study reveals that obesity plays a significant role in establishing a tumor microenvironment that facilitates tumor progression.
Obesity has been linked to several common cancers and it also increases the risk of dying from cancer and may influence treatment choices. Excess body fat results in an approximately 17% increased risk of cancer-specific mortality. In addition to that 4–8% of all cancers are attributed to obesity itself.
“We tend to think about the increased risks for gastrointestinal tumors, breast cancer, pancreatic cancer, and ovarian cancer when it comes to obesity,” lead author Dr. Yu Leo Lei, an associate professor of dentistry in the Department of Periodontics and Oral Medicine at the university, said in a press release. “Multiple recent prospective cohorts involving millions of individuals from several continents revealed a previously underappreciated link between obesity and oral cancer risks,” he continued.
The research team discovered that saturated fatty acids can inhibit the cytosolic DNA-induced STING pathway, which enhances the maturation of antigen-presenting cells by activating the protein NLRC3.
Discussing the findings of the study, he noted: “Myeloid cells in obese mice were insensitive to STING agonists and were more suppressive of T-cell activation compared to the myeloid cells from lean hosts.” This, in turn, weakened anti-tumor immunity in the tumor microenvironment.
A frequent comorbidity among cancer patients is obesity. The Centers for Disease Control and Prevention estimate that about 684,000 malignancies linked to obesity are diagnosed each year in the US. According to recent research, people with oral cancer who were prescribed statins—medications that lower cholesterol—had better 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-tumour immune response,” Dr. Lei stated.
Following up on the study, the researchers will now explore how obesity regulates other immune-activating pathways. Additionally, they will seek to improve oral cancer prevention in high-risk individuals.
You can read the whole report here: “Saturated fatty acids dampen the immunogenicity of cancer by suppressing STING”
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