Promoting APC function of B cells via reprogramming the fatty acid metabolism enhances anticancer immunity in metastatic ovarian cancer

B cells have become one of the important participants in anti-tumor immunity. Compared with DCs and macrophages, B cells have unique advantages in presenting low-abundance antigens to T cells. Fatty acids play a key role in the metabolic adaptation of B cells. Whether the APC function of B cells can be enhanced through reprogramming fatty acid metabolism in the tumor microenvironment (TME) is worthy of study. Ovarian cancer (OvCa) is a gynecological malignant tumor with a high mortality rate. Most patients in the advanced stage often have extensive omental metastasis and ascites formation, which are rich in adipocytes and fatty acids. Given reasons including complex TME, the clinical efficacy of new immunotherapies such as immune checkpoint blockade (ICB) therapy for OvCa is very limited. Therefore, treatment regimens based on new mechanisms are urgently needed to be developed. In this study, we applied the Gene Expression Omnibus (GEO) database, clinical specimens, cell lines, and mouse models to investigate whether reprogramming the fatty acid metabolism in B cells could enhance their APC function and to explore the underlying mechanisms. We also evaluated the therapeutic effects of the combined treatment using APC-enhanced-B cells adoption with low-dose chemotherapy in metastatic OvCa mice. Our research provides new clues forB cells-based anti-tumor immunotherapy.