Obesity-related immune dysfunction linked to increased cancer risk
Researchers at Saint Louis University’s (SLU) School of Medicine have revealed a critical link between immune system dysfunction and an elevated risk of cancer in people living with obesity. The team found that T-cell dysfunction, a key component of immune health, plays a central role in this heightened risk.
T cells, a type of white blood cell classified as lymphocytes, are essential to the body’s immune system, defending against infections and cancer. Dr Ryan Teague, professor of molecular microbiology and immunology at SLU, and his research team are investigating how obesity impacts T-cell function and impairs immune surveillance—the body’s ability to detect and eliminate malignant cells before they develop into tumours.
The team’s findings, published in Nature Communications, were the result of a study led by Dr Teague and co-authored by Alex Piening, an M.D./Ph.D. candidate at SLU. The study demonstrated that obesity-related T-cell dysfunction prevented these immune cells from recognising and attacking tumour cells, resulting in a higher susceptibility to cancer in mice with obesity exposed to carcinogens. Now, the researchers are working to pinpoint the specific metabolic mechanisms associated with obesity that impair T-cell function.
Dr Teague’s lab focuses on identifying obstacles to effective cancer immunotherapy and developing strategies to overcome them, with the goal of improving outcomes for individuals undergoing these treatments. His team is particularly interested in understanding how obesity affects the efficacy of immunotherapies.
“Immunotherapy boosts a patient’s immune system by targeting T cells and reinvigorating them. Paradoxically, immunotherapy is often more successful in patients with obesity, where the immune system isn’t functioning quite as well,” Dr Teague explained. “Our research explains this paradox by showing that, in the context of obesity, developing tumours are only required to evade a weakened immune system. These tumours, therefore, are not as well adapted to escape the reinvigorated T cells stimulated during immunotherapy, making them more vulnerable to destruction.”
The study also highlights the role of advanced technology in achieving these findings. Single-cell RNA sequencing, a technique that allows researchers to examine the activity within individual immune cells, was instrumental in uncovering the details of T-cell dysfunction.
“We learned that the dysfunction in these T cells lies in their inability to kill tumours. The genes responsible for this activity were not being activated,” Dr Teague noted. “Additionally, the cells lacked the ability to acquire the metabolic functions required to sustain anti-tumour activity.”
SLU’s investment in single-cell RNA sequencing technology has been a driving force behind these discoveries. The Department of Molecular Microbiology and Immunology is leveraging this cutting-edge approach to advance its understanding of cancer and the immune system, bringing researchers closer to innovative treatments and potential cures.
This research underscores the complexity of the relationship between obesity, immune function, and cancer risk, while also offering hope for improved immunotherapy strategies tailored to individuals living with obesity.
