Study unmasks how ovarian tumors evade immune system

December 1, 2008

Scientists at Johns Hopkins have determined how the characteristic shedding of fatty substances, or lipids, by ovarian tumors allows the cancer to evade the body's immune system, leaving the disease to spread unchecked. Ovarian cancer is considered to be one of the most aggressive malignancies, killing more than 70 percent of diagnosed women within five years, including an estimated 15,000 this year.

In a two-year series of lab experiments, a team of researchers from the Johns Hopkins University School of Medicine and its Sidney Kimmel Comprehensive Cancer Center showed that fluid secretions from tumors, called ascites, which contain lipids and collect in the space surrounding cancerous ovaries, can totally suppress the action of natural killer T cells in the immune system.

Known as NKTs for short, these special T cells must be activated to do their job of jump-starting the immune response and signaling other kinds of white blood cells to rid the body of diseases or leave healthy tissue alone.

As part of 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.

In a report set to appear in the Dec.1 issue of the journal Clinical Cancer Research, the research team also found this evasive blocking tactic to be virtually exclusive to a specific protein, called CD1d, needed to activate the NKT cells.

Their experiments specifically 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.

Disrupted or stalled T cell action has been known to play a key role in the spread of several kinds of cancer, the scientists say. But until now, there was no firm evidence that tied a specific T cell in the body's defensive immune system to ovarian cancer.

"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," says immunologist and study senior investigator Mathias Oelke, Ph.D.

According to Oelke, an assistant professor at Johns Hopkins, the research is believed to be the first to demonstrate the clinical effect of ascites on human NKT cells and describe the regulatory role of lipids in cancer progression. Previous studies in mice have confirmed that lipids assist in tumor evasion, he notes. But he says this is the first evidence in humans about the immune-suppressing effects of ascites on NKT cells, which 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," says study co-investigator Jonathan Schneck, M.D., Ph.D.
Schneck, a professor of pathology, medicine and oncology, 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.

Moreover, the blocking action only occurred with ascites. Matching blood serum samples from the women with cancer failed to block NKT activation.

Researchers say 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. Their goal, researchers say, is to find links to other diseases and T-cell activity gone awry.

Source: Johns Hopkins Medical Institutions

Explore further: Scientists give tumor-fighting cells a boost in battling bone marrow cancer

Related Stories

Scientists give tumor-fighting cells a boost in battling bone marrow cancer

June 1, 2017
Researchers from Belgium led by Prof. Dirk Elewaut of the VIB-UGent Center for Inflammation Research and the team of Prof. Vanderkerken and Prof. Menu at the Hematology and Immunology lab of the VUB uncovered a new way to ...

Redirecting our immune cells to help fight children's cancer

November 6, 2013
Immune cells, known as Natural Killer T cells, could be redirected to help fight the childhood cancer, neuroblastoma, according to research presented at the National Cancer Research Institute (NCRI) Cancer Conference in Liverpool ...

Researchers find source of new lineage of immune cells

February 12, 2014
The elusive progenitor cells that give rise to innate lymphoid cells—a recently discovered group of infection-fighting white blood cells—have been identified in fetal liver and adult bone marrow of mice, researchers from ...

Scientists discover immune cells could protect against obesity

October 1, 2012
(Medical Xpress)—New research has found that a type of anti-tumour immune cell protects against obesity and the metabolic syndrome that leads to diabetes. Results showing that immune cells known to be protective against ...

Researchers uncover marker important to effectiveness of natural killer T cells

May 17, 2016
Natural killer T cells, or NKT cells, are potent warriors against solid tumor cancers. However, the potential for this small subset of white blood cells has been limited by the lack of understanding of how they can be multiplied ...

Researchers overcome barrier to cancer immunotherapy

September 2, 2011
(Medical Xpress) -- In lab studies, researchers at Virginia Commonwealth University Massey Cancer Center have effectively reprogrammed cells of the innate and adaptive immune system to overcome a key cancer defense mechanism ...

Recommended for you

Study may explain failure of retinoic acid trials against breast cancer

July 25, 2017
Estrogen-positive breast cancers are often treated with anti-estrogen therapies. But about half of these cancers contain a subpopulation of cells marked by the protein cytokeratin 5 (CK5), which resists treatment—and breast ...

Physical activity could combat fatigue, cognitive decline in cancer survivors

July 25, 2017
A new study indicates that cancer patients and survivors have a ready weapon against fatigue and "chemo brain": a brisk walk.

Breaking the genetic resistance of lung cancer and melanoma

July 25, 2017
Researchers from Monash University and the Memorial Sloan Kettering Cancer Center (MSKCC, New York) have discovered why some cancers – particularly lung cancer and melanoma – are able to quickly develop deadly resistance ...

New therapeutic approach for difficult-to-treat subtype of ovarian cancer identified

July 24, 2017
A potential new therapeutic strategy for a difficult-to-treat form of ovarian cancer has been discovered by Wistar scientists. The findings were published online in Nature Cell Biology.

Immune cells the missing ingredient in new bladder cancer treatment

July 24, 2017
New research offers a possible explanation for why a new type of cancer treatment hasn't been working as expected against bladder cancer.

Anti-cancer chemotherapeutic agent inhibits glioblastoma growth and radiation resistance

July 24, 2017
Glioblastoma is a primary brain tumor with dismal survival rates, even after treatment with surgery, chemotherapy and radiation. A small subpopulation of tumor cells—glioma stem cells—is responsible for glioblastoma's ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.