Newswise — Immune system cells called macrophages play an unexpected role in the complicated connection between obesity and cancer, a Vanderbilt University Medical Center-led research team has discovered. Obesity increases the frequency of macrophages in tumors and induces their expression of the immune checkpoint protein PD-1 — a target of cancer immunotherapies. The findings, published June 12 in the journal Nature , provide a mechanistic explanation for how obesity can contribute to both increased cancer risk and enhanced responses to immunotherapy.
They may also suggest strategies for improving immunotherapy and for identifying patients who will respond best to such treatments. “Obesity is the second leading modifiable risk factor for cancer, behind only smoking, and obese individuals have a greater risk for worse outcomes. But they also can respond better to immunotherapy,” said Jeffrey Rathmell, PhD, Cornelius Vanderbilt Professor of Immunobiology and director of the Vanderbilt Center for Immunobiology.
“How is it that there can be this worse outcome on one hand, but better outcome on another? That’s an interesting question.” Postdoctoral fellow Jackie Bader, PhD, led the studies to examine the influence of obesity on cancer and to explore this “obesity paradox” — that obesity can contribute to cancer progression but also improve response to immunotherapy. In a mouse model, the researchers found striking differences between the macrophages isolated f.
