二甲双胍,一种以抗血糖特性而闻名的药物,也证明了有效的免疫系统激活。在我们的研究中,在BALB/CWT小鼠中使用4T1乳腺癌模型,我们检查了二甲双胍对多种免疫细胞功能表型的影响,由于在这种情况下尚未研究过的作用,因此特别强调自然杀伤T(NKT)细胞。二甲双胍给药可延缓癌的出现和生长。此外,二甲双胍增加IFN-γ+NKT细胞的百分比,和增强CD107a表达,以MFI衡量,同时减少PD-1+,FoxP3+,和二甲双胍处理的小鼠脾脏中的IL-10+NKT细胞。在原发性肿瘤中,二甲双胍增加NKp46+NKT细胞的百分比并增加FasL表达,在降低FoxP3+的百分比的同时,PD-1+,和产生IL-10的NKT细胞和KLRG1表达。激活标记增加,来自脾脏和肿瘤的T细胞中的免疫抑制标志物下降。此外,二甲双胍降低IL-10+和FoxP3+Tregs,随着Gr-1+骨髓来源的抑制细胞(MDSCs)在脾,在肿瘤组织中,它降低了IL-10+和FoxP3+Tregs,Gr-1+,NF-κB+,和iNOS+MDSCs,和iNOS+树突状细胞(DC),同时增加DC数量。此外,MIP1a的表达水平增加,在脾细胞中发现了STAT4和NFAT。这些全面的研究结果表明,二甲双胍对多种免疫细胞具有广泛的免疫调节作用。包括刺激NKT细胞和T细胞,同时抑制Tregs和MDSCs。这种动态调节可能会增强其在癌症免疫疗法中的应用,强调其在一系列免疫细胞类型中调节肿瘤微环境的潜力。
Metformin, a medication known for its anti-glycemic properties, also demonstrates potent immune system activation. In our study, using a 4T1 breast cancer model in BALB/C WT mice, we examined metformin\'s impact on the functional phenotype of multiple immune cells, with a specific emphasis on natural killer T (NKT) cells due to their understudied role in this context. Metformin administration delayed the appearance and growth of carcinoma. Furthermore, metformin increased the percentage of IFN-γ+ NKT cells, and enhanced CD107a expression, as measured by MFI, while decreasing PD-1+, FoxP3+, and IL-10+ NKT cells in spleens of metformin-treated mice. In primary tumors, metformin increased the percentage of NKp46+ NKT cells and increased FasL expression, while lowering the percentages of FoxP3+, PD-1+, and IL-10-producing NKT cells and KLRG1 expression. Activation markers increased, and immunosuppressive markers declined in T cells from both the spleen and tumors. Furthermore, metformin decreased IL-10+ and FoxP3+ Tregs, along with Gr-1+ myeloid-derived suppressor cells (MDSCs) in spleens, and in tumor tissue, it decreased IL-10+ and FoxP3+ Tregs, Gr-1+, NF-κB+, and iNOS+ MDSCs, and iNOS+ dendritic cells (DCs), while increasing the DCs quantity. Additionally, increased expression levels of MIP1a, STAT4, and NFAT in splenocytes were found. These comprehensive findings illustrate metformin\'s broad immunomodulatory impact across a variety of immune cells, including stimulating NKT cells and T cells, while inhibiting Tregs and MDSCs. This dynamic modulation may potentiate its use in cancer immunotherapy, highlighting its potential to modulate the tumor microenvironment across a spectrum of immune cell types.