Researchers at Johns Hopkins have exposed the secret behind how ovarian tumors can escape detection by the body's immune system. This lets the cancer spread unimpeded.
Ovarian tumors usually release fatty substances, or lipids in order to avoid detection by the immune system.
In the study, a team of researchers from the Johns Hopkins University School of Medicine and its Sidney Kimmel Comprehensive Cancer Center conducted a two-year series of lab experiments.
They showed that fluid secretions from tumors, called ascites, which contain lipids and collect in the space surrounding cancerous ovaries, could totally suppress the action of natural killer T cells in the immune system.
These special T cells, called NKTs for short, must be activated to trigger the immune response and signal other kinds of white blood cells to rid the body of diseases or leave healthy tissue alone.
For the study, 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 they blocked activation of NKT cells.
The team also found that the evasive blocking tactic was virtually exclusive to a specific protein, called CD1d, needed to activate the NKT cells.
Specifically, the experiments showed that NKT activation was blocked between 10 percent and 100 percent after test cultures of cells that stimulate NKT cells were exposed to increasing concentrations of tumor-derived ascites.
"Our study findings lay out for the first time how ovarian cancer evades a critical check-point in the immune response, opening the door to future drug development that can halt, limit, reverse or even bypass the blockage, permitting CD1d-mediated NKT cell activation," said immunologist and study senior investigator Mathias Oelke, Ph.D.
He said that the research could be the first to show the clinical effect of ascites on human NKT cells and describe the regulatory role of lipids in cancer progression. Also, he claimed the study to be the first evidence in humans about the immune-suppressing effects of ascites on NKT cells.
NKT cells are also abundant in cancers that spread to the abdomen and in other infectious diseases.
"The ultimate goal, of course, is to make sure the immune system can detect the cancer and, we hope, attack and eliminate it," said study co-investigator Jonathan Schneck, M.D., Ph.D. Schneck.
He described the blocking as "rapid and prolonged," happening within four hours of ascites exposure and remaining constant for the test duration.
When ascites extracted from men and women with another disease, hepatitis C, were exposed to cells that stimulate NKT cells, only two of six ascites 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.oreover, the blocking action only occurred with ascites. Matching blood serum samples from the women with cancer failed to block NKT activation.
Researchers have said that their next steps are 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. They said their goal is to find links to other diseases and T-cell activity gone awry.
The study will appear in the latest issue of the journal Clinical Cancer Research.