Human NK cells have massive nuclei stained in blue and droplets of fats shops stained in crimson. Credit score: Dr. Karen Slattery, Trinity School Dublin
New analysis led by Irish scientists has uncovered how lipid-rich fluid within the stomach, generally known as ascites, performs a central position 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 complicated stage, typically presenting with massive 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 essential for growing higher therapies that use the immune system to battle most cancers.
On this examine, researchers from Trinity School Dublin and College School Dublin explored how ascites disrupts immune cell perform, with a specific concentrate on pure killer (NK) cells and T cells, that are key gamers within the physique’s skill to eradicate tumors.
By analyzing the contents of ascites fluid from ovarian most cancers sufferers, the workforce recognized a bunch 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 mentioned, “We discovered that these lipids intervene with NK cell metabolism and suppress their skill to kill most cancers cells. Crucially, we additionally found that blocking the uptake of those phospholipids into NK cells utilizing a selected receptor blocker can restore their anti-tumor exercise, which presents a compelling new goal for therapeutic intervention.”
“This work provides a crucial piece to the puzzle of why ovarian most cancers is so aggressive and has such poor outcomes. Whereas the immune system is of course outfitted to detect and destroy most cancers cells, this perform is switched off in lots of people with ovarian most cancers, and we now know that that is partly as a result of fat-rich setting created by ascites.”
Prof. Lydia Lynch, previously primarily based in Trinity and now in Princeton College, is the senior creator of the analysis article.
She mentioned, “This examine marks a big development in ovarian most cancers analysis, figuring out a brand new mechanism underpinning immune failure and laying the muse for brand spanking new therapies that would restore immune perform in these sufferers.
“By concentrating on the fat-induced suppression of immune cells, future therapies may empower the physique’s personal immune defenses to battle again and, in doing so, enhance outcomes for ovarian most cancers sufferers.”
Extra info:
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 gas immune failure in ovarian most cancers (2025, Could 9)
retrieved 9 Could 2025
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