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Reducing cholesterol could enhance T-cell cancer immunotherapy

Cleveland Clinic researchers have demonstrated for the first time that lowering blood cholesterol levels could enhance the success of a specific type of T-cell immunotherapy in fighting cancer.

The team, led by Qing Yi, MD, PhD, of Cleveland Clinic Lerner Research Institute studied T-cell transfer, which has shown great success in recent years.

Dr. Yi previously showed that a specific subset of T-cells, called Tc9 cells, have stronger anti-tumour effects than other types of T-cells.

In the newly published study, they determined the mechanisms that give Tc9 cells their anti-cancer properties and how those mechanisms might be tweaked to enhance immunotherapy.

Using gene profiling, the researchers discovered that Tc9 cells had much lower levels of intracellular cholesterol than other T-cells.

They hypothesised that the reduced cholesterol levels might contribute to the cells' anti-tumour effects.

Indeed, when cholesterol-lowering drugs were administered to the cells, anti-cancer pathways were turned on (IL-9 expression and NF-KB signalling).

Furthermore, they showed in a tumour-bearing preclinical model that reducing cholesterol levels prior to immunotherapy led to greater concentrations of IL-9 and better cancer-killing success.

Immunotherapy is a type of cancer treatment that harnesses the power of the human immune system to attack and kill cancer cells.

Adoptive T-cell transfer involves transplanting T-cells engineered to recognise a certain type of cancer.

Researchers have focused on many different methods to manipulate and enhance the T-cells' anti-cancer activity, such as transferring cells at different stages of differentiation or using certain drugs in tandem with immunotherapy.

"Our studies suggest a relatively simple, cost effective way to enhance T-cell transfer therapy," Dr. Yi said. "We hope to test our findings in clinical trials soon."

Source: Cleveland Clinic

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