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

为明确长链脂肪酸(LCFAs)对肿瘤免疫微环境的调控作用及机制, 以髓源抑制性细胞(MDSCs)及多种小鼠肿瘤模型为研究对象, 采用体内外LCFAs暴露及高LCFAs饮食干预等方法, 分析LCFAs对MDSCs免疫抑制功能、CD8⁺ T细胞抗肿瘤免疫及肿瘤进展的影响。研究结果表明, 通过在体外和体内采用LCFAs对细胞进行处理, 可以显著地降低单核髓源抑制性细胞(M-MDSCs)和多形核髓源抑制性细胞(PMN-MDSCs)中特征性免疫抑制基因的表达水平。喂食高LCFAs含量饮食的小鼠在不同的癌症模型中均表现出肿瘤进展延缓和生存期延长。此外, 这种LCFAs介导的对M-MDSCs和PMN-MDSCs的抑制作用与增强的CD8⁺ T细胞抗肿瘤免疫相关, 这种效应在荷瘤裸鼠中消失。研究结果揭示了LCFAs在肿瘤免疫微环境中以前未被充分认识的一种作用, 提示癌症治疗的新策略。