Derailing certain cells in immune system can increase tumor-fighting efficiency
By: Benjamin Bian
Drugs that help the immune system fight cancers are undoubtedly effective. However, checkpoint blocker therapies may not be enough to finish the job and sometimes fail in patients. This is because the body’s immune system stalls the deployment of T-cells and other lymphocytes in numerous ways.
Checkpoint blocker therapies commonly target protein interactions that disarm T cells. However, research has found that myeloid-derived suppressor cells, or MDSCs, also slow down the response. With no defense against tumors, the tumors continue to grow until the patient succumbs to cancer. Interestingly, MDSCs grow at alarmingly high rates in people with carcinoma.
However, experiments in mice show that scientists can greatly combat cancer with checkpoint therapy and a cocktail of drugs that derail the effects of MDSCs.MDSCs are immature cells that are related to neutrophils and macrophages, which first respond to infection.
“Their normal function is to slow things down,” says William Carson III. Carson III is a surgical oncologist, a doctor that studies and treats cancer. In 2016, a study of people with advanced melanoma (skin cancer) underwent checkpoint blocker therapy. People with lower counts of MDSCs lived longer than others. This is what prompted Carson III’s research: he found drugs that could replicate this effect, Brd4 inhibitors.
Brd4 is a protein that plays a key role in cancer development, it encourages the growth of MDSCs.Carson III and his team think that if we inhibit these proteins, we can combat inoperable cancer.
In the experiment, scientists tested on mice with ductal carcinoma, or breast cancer. Breast cancer is particularly difficult to treat with checkpoint blocker therapy.3 out of 11 mice treated with checkpoint blocker therapy had slowed tumor growth. However, when mice were treated with Brd4 inhibitors, they did not perform as well as the other mice. Finally, the third group of mice were treated with both combination therapy and Brd-4 inhibitors. These mice performed the most impressive; 7 out of 11 mice had shrinking tumors.
Unfortunately, even though success is obvious in mice, these drugs still have yet to prove in human clinical trials. Many other drugs are testing this theory, but the immune system is a complicated place.