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Lowering cholesterol improves cancer-fighting immunotherapy

A new study has found that when cholesterol levels are reduced, cancer immunotherapy becomes more effective. The findings offer a simple way to improve this fledgling technology.
Cancer researcher in the lab
Lowering cholesterol may improve cancer outcomes in the future.

Immunotherapy is a fairly new but successful method of treating cancer. It uses the body’s own immune system to fight cancerous cells.

Scientists are currently investigating a range of immunotherapies that use a variety of tactics.

Some types work to enhance the body’s natural immune response against cancer cells, and this is known as passive immunization.

Other versions actively direct the immune system to attack specific proteins on cancer cells, and these are called active immunotherapies.

One type of passive immunization — adoptive T cell transfer — involves engineering T cells to home in on a specific cancer type before transplanting them into the patient.

Boosting immunotherapy

Adoptive T cell transfer is still a relatively new technology. In fact, the first two procedures of this type to be used in the United States were only approved by the Food and Drug Administration (FDA) in 2017.

As such, scientists are still working out how to enhance the therapy and make it as effective as possible. For instance, researchers are currently investigating the use of different methods to transplant the T cells, as well as how combining the therapy with other drugs might improve outcomes.

Dr. Qing Yi, Ph.D., from the Cleveland Clinic Lerner Research Institute in Ohio, is approaching this question from a slightly different angle. He is interested in how cholesterol may play a part in the success of adoptive T cell transfer.

The latest study from his laboratory is now published in the Journal of Experimental Medicine.

In previous work, Dr. Yi identified that a specific subtype of T cell — Tc9 cells — were more fiercely anti-cancer than others. Tc9 cells are known to excrete interleukin 9 (IL 9), a signaling molecule with anti-tumor properties.

Building on this finding, Dr. Yi wanted to understand whether Tc9 cells could be enhanced further.

Cholesterol may be the key

Using gene profiling — a technique that allows scientists to see which genes are “switched on” in a cell — they compared Tc9 cells with other subtypes of T cell. They found that Tc9 cells contained significantly less cholesterol.

This, they thought, might be key to their improved cancer-fighting ability. So, they took their hunch to the laboratory and put it to the test.

To investigate, they added cholesterol-lowering drugs to cancer cells before treating them. As they expected, this had the effect of turning on anti-cancer pathways.

In a second part of the study, they used a tumor-bearing animal model. They discovered that, when cholesterol levels were reduced before the course of immunotherapy began, there was a greater expression of IL 9, and its anti-tumor effects were more pronounced.

As the study authors explain, “Our study identifies cholesterol as a critical regulator of Tc9 cell differentiation and function.”

Dr. Yi is excited about the findings. He says, “Our studies suggest a relatively simple, cost-effective way to enhance T cell transfer therapy.” The scientists plan to continue their line of investigation and embark on clinical trials as soon as possible.

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