Source: Duke University Medical Center
Summary: Researchers have tracked the missing T-cells in glioblastoma patients. The findings open a new area of exploration for adjunct cancer drugs that could free trapped T-cells from the bone marrow and improve existing immunotherapies.
Glioblastoma brain tumors can have an unusual effect on the body’s immune system, often causing a dramatic drop in the number of circulating T-cells that help drive the body’s defenses. Where the T-cells go has been unclear, even as immunotherapies are increasingly employed to stimulate the body’s natural ability to fight invasive tumors. Now researchers at Duke Cancer Institute have tracked the missing T-cells in glioblastoma patients. They found them in abundance in the bone marrow, locked away and unable to function because of a process the brain stimulates in response to glioblastoma, to other tumors that metastasize in the brain and even to injury. The findings open a new area of exploration for adjunct cancer drugs that could free trapped T-cells from the bone marrow, potentially improving the effectiveness of existing and new immunotherapies. The study findings were published in the journal Nature Medicine.
The research team began its search for the missing T-cells after observing that many newly diagnosed glioblastoma patients have the equivalent immune systems of people with full-blown AIDS, even before they undergo surgery, chemotherapy and radiation. Where most people have a CD-4 “helper” T-cell count upwards of 700-1,000, a substantial proportion of untreated glioblastoma patients have counts of 200 or less, marking poor immune function that makes them susceptible to all manner of infections and potentially to a progression of their cancer. When examining the stashed T-cells, they found that they lacked a receptor on the cell surface called S1P1, which essentially serves as a key that enables them to leave the bone marrow and lymph system. Lacking that key, they instead get locked in, unable to circulate and fight infections, let alone cancer. The team is now working to learn exactly how the brain triggers the dysfunction of this S1P1 receptor. He said the current theory is that the receptor somehow is signaled to retract from the cell surface into the cell interior.
Lead author, Peter E. Fecci, M.D., Ph.D., said, “We are hopeful that this finding provides a missing element that would enable more immunotherapies to be effective for more people” and further added, “the finding could also work in reverse, offering a new approach to quell auto-immune disorders by activating the T-cell sequestration”.
More Information: Sequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors, Nature Medicine (2018). DOI: 10.1038/s41591-018-0135-2