Fat-rich fluid fuels immune failure in ovarian cancer

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 defences. Understanding how ascites affects the immune system is important for developing better treatments that use the immune system to fight cancer.

In this recent study, researchers from Trinity College Dublin and University College Dublin explored how ascites disrupts 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 tumours.

By analysing 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, Research Fellow in the Trinity Translational Medicine Institute, is the first author of the research article just published in 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-tumour 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 in Trinity and now in 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 defences to fight back and in doing so, improve outcomes for ovarian cancer patients.”