The researches find that the A checkpoint may delay travelers but it can help give cancer free rein by suppressing the natural immune response that should destroy it, researchers say. Because Now they want to learn more about how the enzyme CD73 an abundant checkpoint in our body that helps keep our immune system from getting; out of control is helping often-aggressive head and neck cancers thrive.
Natural immune response
CD73 is found in all cells and in abundance in the supportive microenvironment of head and neck cancers. Therefore High levels already are associated with poor prognosis in the most common type of these cancers. Immunologist Dr. Yan Cui and colleagues otolaryngologists Drs. Michael Groves and J. Kenneth Byrd want to know more about where high levels originate with the long-term goal of blocking them.
One way CD73 appears to support cancer is by converting the cell fuel ATP; or adenosine triphosphate, which typically works to activate the immune response; back to adenosine, but a natural compound that inhibits it, says Cui; a member of the Cancer Immunology; Therefore Inflammation and Tolerance Research Program at the Georgia Cancer Center and professor in the Department of Biochemistry and Molecular Biology at the Medical College of Georgia at Augusta University.
Converting the cell fuel
That key action makes CD73 an immune checkpoint and potential treatment target in the most common head and neck cancers; called squamous cell carcinomas, the researchers say. Cui is principal investigator on a $420,000, two-year Exploratory/Developmental Research Grant from the National Institute of Dental and Craniofacial Research that is providing more insight into how CD73 supports cancer.
Most of the help seems to come from the environment the tumor has built to support itself, called the tumor microenvironment. Cui has shown that in the microenvironment; stromal cells like fibroblasts, express high levels of CD73, which helps create a perfect storm that ultimately helps cancer cells survive.
Stromal cells like fibroblasts
These cancer-associated fibroblasts seem to be particularly adept at making CD73 and Cui has found high levels of fibroblasts can mean low levels of T cells; key drivers of the immune response. In fact; Cui has seen in some head and neck cancers a large number of immune cells clearly present and clearly not functioning “They are there, but they are tolerant;” Cui says, while in other tumors; immune cells are just MIA. “CD73 very rapidly gets rid of the ATP and changes it to the immunosuppressive adenosine;” says Cui of the powerful immune checkpoint. “Adenosine; in turn, can inhibit T cell function; in very high concentrations it can even kill the T cells,” she says.