SLU Study: Immune Dysfunction Increases Cancer Risk in Obese Populations

11/14/2024

ST. LOUIS —Researchers at Saint Louis University’s 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 infection and disease. However, SLU researchers are exploring how obesity impacts T-cell dysfunction and compromises immune surveillance, or the body’s ability to survey malignant cells and clear them before they become tumors. 

"'How' is the $1,000,000 question," said Ryan Teague, Ph.D., professor of molecular microbiology and immunology at SLU, the paper’s lead author. “However, we know that increased risk for cancer in obese populations is reversible.”

The study, recently published in Nature, found that T-cell dysfunction is linked to diet and metabolic health rather than body mass typically associated with obesity. Teague and his team are trying to uncover the exact mechanism of the metabolic dysfunctions associated with obesity that directly impact immune function.

Ongoing projects in Teague’s 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. 

In this study, Teague and his team have shown that obese cancer populations will respond better to immunotherapies.

"Immunotherapy boosts a patient's immune system by targeting T cells and reinvigorating them," he said. "In the case of obesity, where the immune system isn’t functioning quite well, that leads to the outgrowth of a tumor that was more immunogenic because they weren't being cleared by the tumor cells, so those immunogenic tumor cells responded better."

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

"We learned where 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 divide, proliferate, and survive," he said.

Thanks to SLU’s 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, Saint Louis University School of Medicine; Alexander Piening, 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, Saint Louis University School of Medicine.