Ludwig Cancer Research: The skinny on fat, ascites and anti-tumor immunity

“A Ludwig Cancer Research study has identified a key mechanism by which advanced ovarian cancers suppress anti-tumor immune responses and resist immunotherapies. Led by Ludwig Princeton’s Lydia Lynch and reported in the current issue of Science Immunology, the study details how ascites fluid—produced in large quantities as ovarian cancer spreads from the ovaries into the abdomen and its organs—sabotages cytotoxic lymphocytes, a class of immune cells that kill cancer cells.

“Although ascites fluid has long been known to be immunosuppressive, it has not been clear what precisely gives it that property,” explained Lynch. “We discovered through the large-scale analysis of metabolic building blocks and byproducts in ascites that certain types of fat, or lipids, found at high levels in the fluid cripple three types of cytotoxic lymphocytes: natural killer (NK) cells, T cells and innate T cells. Our studies also identify a mechanism of lipid import employed by NK cells that drives this dysfunction, and provide evidence suggesting it might be targeted for immunotherapy against ovarian cancer.”

Owing to the vagueness of symptoms and the lack of reliable screening tests, more than 70% of women already have metastatic disease by the time they are diagnosed with high-grade serous ovarian cancer (HGSOC). This partly accounts in part for why only about 10-15% of HGSOC patients evaluated in clinical trials have responded to immune checkpoint blockade, a type of immunotherapy that stimulates a T cell assault on tumors.”

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Research led by Karen Slattery