Engineered T-cell therapies, a promising way to “prime” a patient’s immune system against cancer, don’t work for everyone. Scientists from the Medical University of South Carolina (MUSC) found one possible explanation that can be targeted: blood platelets.
The immune system sees tumors, or uncontrolled cell growth, as part of the “self,” which allows cancer to evade immune attack. In adoptive T-cell therapy, a patient’s own T cells are isolated from his or her blood, and then “primed” to recognize tumor cells.
Previous research has shown that some cancers curb T-cell activity and that platelets, a component of blood responsible for clotting, might make cancer worse. The MUSC team, led by senior author Zihai Li, M.D., Ph.D., found that platelets help cancer to hide by secreting a molecule, TGF-beta, that suppresses T cells.
While most TGF-beta is inactive, the researchers found that GARP, a molecular “hook” on the surface of platelets, traps and activates TGF-beta. As a result, platelets become the main source of TGF-beta used by tumor cells to tamp down on T-cell function, according to a statement.
The team ran a battery of preclinical trials, finding that a T-cell therapy more effectively “awoke” the immune system when given alongside common antiplatelet drugs, such as aspirin.
First, they noticed that melanoma tumors grew more slowly in mice with defective platelets than in mice with normal platelets. Adoptive T-cell therapy was more effective in genetically modified mice without GARP. And mice with normal platelets and melanoma that were given T-cell therapy along with aspirin and clopidogrel survived longer and relapsed less, according to the statement. But antiplatelet drugs alone did not fight the cancer.
"We can test simple, over-the-counter antiplatelet agents to really improve immunity and make a difference in how to treat people with cancer,” Li said. The study was published in Nature Immunology.
This study could lay the foundation for further work testing antiplatelet approaches in melanoma and other cancers. Melanoma is not currently treated with adoptive T-cell therapy, but with checkpoint inhibitors, such as Bristol-Myers’ Opdivo and Yervoy.