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SLU Study: Immune Dysfunction Increases Cancer Risk in Obese Populations

11/14/2024

ST. LOUIS 鈥擱esearchers at 老司机福利网鈥檚 School of Medicine say T-cell dysfunction is leading to an increased risk of cancer in obese populations. 

T cells are white blood cells called lymphocytes essential to your immune system in the fight against infections and cancer. Ryan Teague, Ph.D., professor of molecular microbiology and immunology at SLU, and his team are exploring why obesity impacts T-cell dysfunction and compromises immune surveillance, or the body鈥檚 ability to survey malignant cells and clear them before they become tumors.

The study, which was led by Teague and co-authored by Alex Piening, an M.D./Ph.D. graduate student at SLU, was recently published in , found that T-cell dysfunction linked to obesity prevented T cells from detecting tumor cells, placing obese mice at higher risk of developing tumors when exposed to a carcinogen. Teague and his team are now trying to uncover the exact mechanism underlying the metabolic dysfunctions associated with obesity that directly impact T-cell function. 

Ongoing projects in Teague鈥檚 lab at SLU are designed to identify barriers to successful cancer immunotherapy and develop strategies to overcome these barriers for improved patient outcomes. Teague and his team investigate how obesity impacts 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鈥檛 functioning quite as well," Teague said. "Our research explains this paradox by showing that in the setting of obesity, developing tumors are only required to escape a weakened immune system. Such outgrown tumors are not well adapted to evade the reinvigorated T cells elicited during immunotherapy, and thus, are more easily destroyed."

Teague said single-cell RNA sequencing played a critical role in the study鈥檚 findings, which allowed scientists to learn what鈥檚 happening inside individual immune cells within tumors.

"We learned that the dysfunction in these T cells lies in their inability to kill tumors. Those genes were not being turned on. It also lies in their inability to acquire the metabolic functions needed to sustain anti-tumor activity," Teague said.

Thanks to SLU鈥檚 investment in single-cell RNA sequencing technology, the Department of Molecular Microbiology and Immunology has leveraged this new approach to advance its work studying cancer and the immune system, bringing us closer to new cures.

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Other authors include Kelly D. Pyles, Kyle S. McCommis, Ph.D., Department of Biochemistry and Molecular Biology, 老司机福利网 School of Medicine; Emily Ebert, Carter Gottlieb, Niloufar Khojandi, Lindsey M. Kuehm, Stella G. Hoft, Richard J. DiPaolo, Ph.D., Stephen T. Ferris, Ph.D., Elise Alspach, Ph.D., Department of Molecular Microbiology and Immunology, 老司机福利网 School of Medicine.