Produced copiously as ovarian tumors spread into the abdomen, ascites fluid is known to be immunosuppressive. But why it is so was not clear. Researchers led by Ludwig Princeton’s Lydia Lynch reported in a May 9 publication in Science Immunology one significant reason this is the case: certain lipids found at high levels in ascites cripple natural killer (NK) cells, T cells and innate T cells. Lydia and her colleagues—including senior author Marcia Haigis of Ludwig Harvard—discovered that lymphocytes isolated from ovarian tumors and metastases produce very low levels of perforin and granzyme B, which kill target cells. Metabolic analyses and other studies revealed that while ascites is rich in nutrients, some of its fats cause lymphocyte dysfunction. NK cells, in particular, are so overwhelmed by the influx of polar lipids—especially phosphatidylcholine (36:1)—that they become incapable of handling, storing and processing fats. This undermines their ability to take up and use amino acids and glucose, which disrupts their cytotoxic machinery and production of stimulatory immune factors like IFNγ and TNFα. Depleting lipids from ascites restored the glucose uptake and cytotoxic function of NK cells. The researchers also identified a lipid transporter, SCARB1, behind the dysfunction. Blocking SCARB1 restores the cytotoxicity of NK cells in culture even when they’re bathed in malignant ascites, suggesting a therapeutic strategy for further study.
Uptake of lipids from ascites drives NK cell metabolic dysfunction in ovarian cancer
Science Immunology, 2025 May 9