Ascites in High Grade Serous Ovarian Cancer (HGSOC): An important new study 

Research Spotlight

May 2025

A (opens in a new window)new study published recently in the high-impact journal Science Immunology has shown that lipids within the ascites fluid of ovarian cancer patients play a key role in altering the local immune environment and allowing for tumours to escape the bodies' natural defences.

This study was led by Prof. Donal Brennan (Systems Biology Ireland, Mater Misericordiae University Hospital) and (opens in a new window)Prof. Lydia Lynch (Princeton, Trinity College Dublin) along with collaborators in Boston and Marseille.

Ovarian cancer patients often develop large accumulations of abdominal fluid (ascites) which have previously been shown to play an important role in driving tumour spread. By examining the ascites from 8 patients with high grade serous ovarian cancer (HGSOC), the study authors found that this fluid exerted a significant immunosuppressive effect on lymphocytes. In particular, they found that a type of lymphocyte with important anti-tumour effects, called Natural Killer (NK) cells, had lower activity and suppressed function when cultured in samples of patient’s ascites.

Further analysis identified a particular lipid, called phosphatidylcholine (36:1) as the key driver of this effect. This lipid is taken up from the ascites by NK cells through the SR-B1 transporter, where it alters the cells activity and leads to a loss of its anti-tumour activity. Blocking this transporter was found to restore normal function of NK cells, suggesting a potential new avenue for immunotherapy development.

The importance of this study is underlined by the great need for improved treatment options for ovarian cancer. With a 5-year survival rate of just 28%, and over 70% of patients presenting with metastatic disease at diagnosis, HGSOC represents a major health burden. Additionally, trials of immunotherapy drugs in ovarian cancer have met with mixed results, highlighting a real need to better understand the unique immunology of the ovarian cancer microenvironment. The identification of the transporter SR-B1 as a central mediator of lipid-driven immunosuppression within ovarian cancer could point towards a novel therapeutic strategy. 

“Immunotherapy which has revolutionised the care of some cancers, has not yielded the same positive results in ovarian cancer”, said study lead-author

This study received supported from (opens in a new window)Research Ireland, through the (opens in a new window)Precision Oncology Ireland consortium, as well as (opens in a new window)the Irish Cancer Society and (opens in a new window)the National Maternity Hospital Foundation.