To clarify the regulatory role and underlying mechanism of long-chain fatty acids (LCFAs) in the tumor immune microenvironment, this study focused on myeloid-derived suppressor cells (MDSCs) and various mouse tumor models. By employing in vitro and in vivo LCFA exposure and high-LCFA diet interventions, we analyzed the effects of LCFAs on the immunosuppressive function of MDSCs, CD8⁺ T cell-mediated anti-tumor immunity, and tumor progression. The results demonstrated that treating cells with LCFAs both in vitro and in vivo significantly decreased the expression levels of characteristic immunosuppressive genes in monocytic MDSCs (M-MDSCs) and polymorphonuclear MDSCs (PMN-MDSCs). Animal experiments showed that mice fed a high-LCFA diet exhibited delayed tumor progression and prolonged survival across different cancer models. Furthermore, this LCFA-mediated inhibition of M-MDSCs and PMN-MDSCs correlates with enhanced CD8⁺ T antitumor immunity, which is abolished in tumor-bearing nude mice. These results reveals a previously under-recognized role of LCFAs in the tumor immune microenvironment, implicating novel therapeutic strategies for cancer treatment. 

Long-chain fatty acids (LCFAs), tumor immune microenvironment, myeloid-derived suppressor cells (MDSCs), antitumor immunity