Discovery of CTLA-4 in dendritic cells opens new possibilities to fight cancer

Source: Baylor College of Medicine, April 2016

T cells are the ‘foot soldiers’ that fight cancer inside the body. Cancer cells can fight the foot soldiers back by pushing a brake on the T cells that will turn them off. This ‘brake’ is a molecule on the surface of T cells called CTLA-4. Until now, most scientists agreed that CTLA-4 was only present on T cells and other cells of the same lineage. But Baylor College of Medicine researchers have discovered that CTLA-4 is also produced and secreted by dendritic cells, which are the ‘generals’ of the T cells in the battle against cancer. The results appear in Stem Cells and Development.

“These results are relevant to the battle against cancer because we showed that dendritic cell CTLA-4 performs a very critical regulatory function. Its presence inhibits the generation of downstream anticancer responses, whereas its absence permits robust priming of such responses. These new data provide a strong rationale to use the drug ipilimumab in new and better ways, for instance in conjunction with cancer vaccines,” said Dr. William K. Decker, assistant professor of pathology & immunology at Baylor and the Center for Cell and Gene Therapy, a member of the Dan L Duncan Comprehensive Cancer Center, and senior author of this paper.

Ipilimumab is a Food and Drug Administration-approved drug to treat melanoma. Scientists think that ipilimumab helps the body fight cancer cells by removing the ‘brake’ cancer cells place on the T cells. Ipilimumab binds to CTLA-4 on T cells, blocking signals that turn off the T cells. As a result, scientists think, T cells resume their fight against the cancer.