Evasive cancer blocking tactic found mainly in CD1d protein, according to Clinical Cancer Research study.
Scientists have determined how the characteristic shedding of fatty substances by ovarian tumors allows the cancer to evade the body’s immune system, leaving the disease to spread unchecked. In a two-year series of lab experiments, investigators showed that the fluid secretions, called ascites, can totally suppress the action of natural killer T (NKT) cells in the immune system.
The team also found that one protein in particular, cluster of differentiation 1 (CD1d), was almost exclusively responsible for the impediment.
Researchers collected lipid-filled ascites from 25 women with ovarian cancer and then exposed the lipid samples to an immune-system test to see if the ascites blocked the activation of NKT cells. The experiments showed that NKT activation was indeed blocked between 10 % and 100 % after test cultures of cells that stimulate NKT cells were exposed to increasing concentrations of the tumor-derived ascites.
According to the investigators, this is the first demonstration of the clinical effect of ascites on human NKT cells that describes the regulatory role of lipids in cancer progression. Previous studies in mice have confirmed that lipids assist in tumor evasion, but this is the first evidence in humans regarding the immune-suppressing effects of ascites on NKT cells, which are abundant in cancers that spread to the abdomen and in other infectious diseases.
When ascites extracted from men and women with hepatitis C were exposed to cells that stimulate NKT cells, only two of the six samples blocked its activation. And in another experiment, immune system CD8 killer T cells functioned normally, even when their stimulator cells were previously treated with ascites.
The investigators noted that the blocking action only occurred with ascites. Matching blood serum samples from the women with cancer failed to block NKT activation.
The team’s next step is to evaluate more than a dozen varieties of lipids that exist in the body to determine their specific role, if any, in modulating the blocking of the NKT cell immune response.
Research for this study, which appears in the December 1 issue of Clinical Cancer Research, was conducted by scientists at the Johns Hopkins University School of Medicine and its Sidney Kimmel Comprehensive Cancer Center.
