Tumor lipids suppress NK cells

Abstract

Patients with peritoneal metastasis can develop ascites, the collection of fluid in the abdomen. Although this has been linked to tumor growth, the mechanisms by which ascites suppresses anti-tumor immunity are unclear. In Science Immunology, Slattery et al. find that natural killer (NK) cells uptake lipids from ascites and this drives NK cell dysfunction, which may contribute to immune suppression in high-grade serous ovarian cancer (HGSOC). In samples from patients with HGSOC, the authors found NK cells in ascites, and these, in addition to NK cells from primary and metastatic tumors, expressed low levels of the activation markers perforin and granzyme B. When NK cells from healthy donors were cultured with ascites from individuals with HGSOC, the tumor killing capacity of NK cells was impaired, the uptake of lipids by NK cells was increased, and there was dysregulation of lipid storage. If lipids were depleted from ascites before culture, NK cell tumor killing capacity was restored. Specifically, phosphatidylcholine (36:1) was present in ascites and accumulated in NK cells, where it caused disruption to the plasma membrane order. The lipid transporter SR-B1 was expressed by NK cells from ascites. If SR-B1 was blocked during culture of ascites and NK cells, there was partial recovery in plasma membrane order, increased expression of cytotoxic molecules and tumor cell killing capacity was improved.

Original reference: Sci. Immunol. 10, eadr4795 (2025)