Harnessing lipid-driven immuno-metabolic pathways in omental metastases to enhance immunotherapy in ovarian cancer

Despite the potential of immune checkpoint blockade (ICB) in epithelial ovarian carcinoma (EOC), its clinical efficacy remains limited. Our study investigates the immuno-metabolic landscape of omental metastases to identify therapeutic targets. Using patient-derived explants (PDEs), we demonstrate that lipid-rich omental environments preserve effector T cell function, while lipid processing in tumor-associated macrophages (TAMs) induces oxidative stress and immune suppression. Targeting lipid metabolism via CCR5 inhibition (e.g., maraviroc) or anti-CD36 treatment reprograms TAMs, restores T cell activity, and enhances anti-tumor immunity. These findings reveal a metabolic-inflammatory axis that can be modulated to improve ICB outcomes in EOC. Overall design: Following MDA-MB-231 tumor growth in MISTRG humanized mice, we perfored scRNA-sequencing analysis on human tumor-infiltrating immune cells to analyse the effects of Maraviroc on the antitumor immune response. In total, cells from 7 treated mice and 7 untreated mice were sequenced after hashing.