Human NK cells have giant nuclei stained in blue and droplets of fats shops stained in purple. Credit score: Dr. Karen Slattery, Trinity Faculty Dublin
New analysis led by Irish scientists has uncovered how lipid-rich fluid within the stomach, referred to as ascites, performs a central function in weakening the physique’s immune response in superior ovarian most cancers. The findings supply new insights into immune suppression in ovarian most cancers and open promising avenues for future immunotherapy approaches.
Over 70% of sufferers with ovarian most cancers are identified at a sophisticated stage, usually presenting with giant volumes of ascites. This ascites fluid not solely helps the unfold of most cancers all through the belly cavity but additionally considerably impairs the physique’s immune defenses.
Understanding how ascites impacts the immune system is necessary for creating higher remedies that use the immune system to struggle most cancers.
On this examine, researchers from Trinity Faculty Dublin and College Faculty Dublin explored how ascites disrupts immune cell operate, with a specific deal with pure killer (NK) cells and T cells, that are key gamers within the physique’s capability to eradicate tumors.
By analyzing the contents of ascites fluid from ovarian most cancers sufferers, the group recognized a gaggle of fats molecules referred to as phospholipids as key drivers of this immune dysfunction.
Dr. Karen Slattery, Analysis Fellow on the Trinity Translational Drugs Institute, is the primary creator of the analysis article printed in Science Immunology.
She stated, “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, previously based mostly in Trinity and now in Princeton College, is the senior creator of the analysis article.
She stated, “This examine marks a major development in ovarian most cancers analysis, figuring out a brand new mechanism underpinning immune failure and laying the inspiration for brand new therapies that might restore immune operate in these sufferers.
“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.”
Extra data:
Karen Slattery et al, Uptake of lipids from ascites drives NK cell metabolic dysfunction in ovarian most cancers, Science Immunology (2025). DOI: 10.1126/sciimmunol.adr4795. www.science.org/doi/10.1126/sciimmunol.adr4795
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Fats-rich fluid discovered to gasoline immune failure in ovarian most cancers (2025, Could 9)
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