Deactivating an Immune Cell Population Could Help Fight Cancer

By: Leyuan Zhou

An immune cell population called Myeloid-Derived Suppressor Cells, or MDSCs, has the ability to stall against checkpoint blockers, a drug treatment that releases brakes on the immune system in people with cancers. Producing a drug that targets them could potentially prevent tumor growth.

Checkpoint blockers usually focus on the protein interactions that help disarm the body’s T-cells, the lymphocytes that cause the cancer to grow in a patient unchecked. However, an additional brake, the Myeloid-Derived Suppressor Cells (MDSCs), is at work as well, and is abundant in people with cancer.

A mix of immature cells, belonging to the same family as neutrophils and macrophages, form the MDSCs. These general first responders in the immune system, which caught scientists’ attention decades ago, came into focus only recently because of their significance in cancer.

“Their normal function is to slow things down,” said William Carson III, a surgical oncologist at Ohio State University in Columbus. Carson thought disabling the MDSCs might allow for a quicker immune response to cancer cells.

In the cells of tumors, Brd4, a protein, regulates the activity of different genes, including some that promote MDSCs. So perhaps a drug that impedes Brd4 would allow checkpoint blockers to perform better.

In an experiment conducted by Andrew Stiff, a physician at Carson's lab, scientists implanted a breast tumor in the bodies of mice. Breast cancer is a type of human cancer that responds poorly to checkpoint blockade. The group of mice that received a combination therapy of anti-PDL1 and a Brd4 inhibitor, aimed to release the brakes on T cells and curb the suppressor cells at the same time, saw successful results. Tumors shrank in seven out of the eleven of those mice.

Similar results emerged with several different Brd4 inhibitors in experiments of mice with breast, colon, and lung tumors. Other experiments suggested Brd4 inhibitors can influence MDSCs in many ways, including directly killing them or suppressing the molecule causes their growth and expansion.

There are also other ways to target these suppressor cells. Timothy Wang, a gastroenterologist at Columbia University Irving Medical Center, and his colleagues tried using an anti-inflammatory peptide called trefoil factor 2, or TFF2, in an experiment with mice.

A combination of TFF2 and anti-PD1 shrank tumors in all five mice with aggressive colorectal cancer.

“However, a drug’s effectiveness in mice has traditionally shown little correlation with its impact in human patients,” states Science News. There is still a need for more experimentation to be done before scientists come to a definite conclusion.

Over a thousand other trials are currently evaluating checkpoint blockers, alone or used with additional drugs, and some are showing some promise.

Article source: https://www.sciencenews.org/article/cells-slow-immune-response-derailing-fight-tumors

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