Researchers from the University of Michigan Rogel Cancer Center and School of Dentistry have recently reported that obesity is responsible for helping to establish a tumour microenvironment that promotes tumour progression. The study found that excessive saturated fat accumulation affects certain oral cancers’ ability to evade attacks from the immune system, thus promoting immune escape and thereby increasing tumour burden.
“We tend to think about the increased risks for gastro-intestinal tumours, 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 team found that saturated fatty acids can block the stimulator of interferon genes (STING) pathway, which is induced by cytosolic DNA and promotes antigen-presenting cell maturation by inducing a protein called 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-tumour immunity in the tumour microenvironment.
Obesity is a common comorbidity in cancer patients. According to the Centers for Disease Control and Prevention, more than 684,000 obesity-associated cancers occur in the US each year.
Recent studies found that oral cancer patients who were on statins, which are medicines that lower cholesterol, had 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,” 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.
The study, titled “Saturated fatty acids dampen the immunogenicity of cancer by suppressing STING”, was published online in the April 2023 issue of Cell Reports.
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