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 infections and cancer. SLU researchers are exploring why 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.

"Human obesity is associated with a higher risk of cancer. 'Why' is the $1,000,000 question," said Ryan Teague, Ph.D., professor of molecular microbiology and immunology at SLU, the paper's lead author.

The study, which was co-authored by Alex Piening, an M.D./Ph.D. graduate student at SLU, was recently published in Nature Communications, 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'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.

"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," he 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's findings, which allowed scientists to learn what's 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," 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; 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.