Ascites Weakens Immunity in Ovarian Cancer Patients
Over 70% of patients with ovarian cancer are diagnosed at an advanced stage, often presenting with large volumes of ascites.
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New research led by Irish scientists has uncovered how lipid-rich fluid in the abdomen, known as ascites, plays a central role in weakening the body’s immune response in advanced ovarian cancer. The findings offer new insights into immune suppression in ovarian cancer and open promising avenues for future immunotherapy approaches
Over 70% of patients with ovarian cancer are diagnosed at an advanced stage, often presenting with large volumes of ascites. This ascites fluid not only supports the spread of cancer throughout the abdominal cavity but also significantly impairs the body’s immune defenses.
Understanding how ascites affect the immune system is important for developing better treatments that use the immune system to fight cancer.
In this recent study, researchers from Trinity and University College Dublin explored how ascites disrupt immune cell function, with a particular focus on natural killer (NK) cells and T cells, which are key players in the body’s ability to eliminate tumors.
By analyzing the contents of ascites fluid from ovarian cancer patients, the team identified a group of fat molecules called phospholipids as key drivers of this immune dysfunction.
Dr. Karen Slattery, a research fellow in the Trinity Translational Medicine Institute, is the first author of the research article just published in the leading international journal Science Immunology.
She said: “We found that these lipids interfere with NK cell metabolism and suppress their ability to kill cancer cells. Crucially, we also discovered that blocking the uptake of these phospholipids into NK cells using a specific receptor blocker can restore their anti-tumor activity, which offers a compelling new target for therapeutic intervention.”
“This work adds a critical piece to the puzzle of why ovarian cancer is so aggressive and has such poor outcomes. While the immune system is naturally equipped to detect and destroy cancer cells, this function is switched off in many individuals with ovarian cancer, and we now know that this is in part due to the fat-rich environment created by ascites.”
Prof. Lydia Lynch, formerly based at Trinity and now at Princeton University, is the senior author of the research article. She said: “This study marks a significant advancement in ovarian cancer research, identifying a new mechanism underpinning immune failure and laying the foundation for new therapies that could restore immune function in these patients. By targeting the fat-induced suppression of immune cells, future treatments could empower the body’s own immune defenses to fight back and in doing so, improve outcomes for ovarian cancer patients.”
This study was funded by the Irish Cancer Society, the National Institutes of Health, Research Ireland (formerly Science Foundation Ireland, under the Strategic Research Programme Precision Oncology Ireland), the Ireland East Hospital Group, the National Maternity Hospital Foundation, the Health Research Board, the Ludwig Center at Harvard, the Glenn Foundation for Medical Research, the Gene Lay Institute, and an AACR Anna D. Barker Basic Cancer Research Fellowship.
Reference: Slattery K, Yao CH, Mylod E, et al. Uptake of lipids from ascites drives NK cell metabolic dysfunction in ovarian cancer. Sci Immunol. 2025;10(107):eadr4795. doi: 10.1126/sciimmunol.adr4795
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