Basirjafar Pedram, Jafarzadeh Abdollah, Salimian Jafar
Applied Virology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Department of Immunology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
Immunol Res. 2024 Dec 10;73(1):2. doi: 10.1007/s12026-024-09564-8.
Leptin, an immune-regulating protein, enhances the maturation of dendritic cells (DCs). We previously demonstrated that leptin and lipopolysaccharide (LPS) promote the expression of co-stimulatory molecules on the surface of DCs. Leptin/LPS-treated DCs increased T cell responses against 4T1 breast cancer in mice. Therefore, in the present study, we investigate the effects of a DC vaccine treated with leptin and LPS on the genes involved in tumor metastasis, angiogenesis, and related cytokines in a mouse model of breast cancer. Tumor induction was achieved through subcutaneous injection of 4T1 cells into syngeneic mice. On days 12 and 19, the mouse groups received the DC vaccine treated with leptin and a combination of leptin and LPS. After sacrificing the mice on day 26, the levels of IL-6 and IL-33 in the serum were assayed using the ELISA technique, and the expression levels of the VEGF, CCL2, MMP9, and CCL5 genes in the tumors were measured by Real-Time PCR. Compared to untreated tumor-bearing mice, the leptin-treated mature DC (mDC) group exhibited a significant reduction in the expression of MMP9 (0.33-fold, p = 0.01) and CCL5 (0.81-fold, p = 0.02). The leptin-LPS-treated mDC group showed decreased expression of genes involved in metastasis and tumor growth, including VEGF (0.72-fold, p = 0.03), MMP9 (0.26-fold, p = 0.001), and CCL5 (0.3-fold, p = 0.006), indicating more efficient prevention of metastasis. The CCL2 gene expression levels in both treatment groups showed a slight decreasing trend, but these changes were not statistically significant. The leptin-treated mDC group reduced IL-6 production by approximately 16% (p = 0.02), while treatment with the leptin-LPS-treated mDC significantly decreased IL-6 production by approximately 22% (p = 0.01) and increased IL-33 production by approximately 42% (p = 0.03). The findings of the present study indicate that the leptin-LPS-treated mDC vaccine group reduced the expression of genes and cytokines involved in metastasis and angiogenesis, demonstrating greater efficacy compared to the leptin-treated mDC vaccine group.
瘦素是一种免疫调节蛋白，可促进树突状细胞（DCs）的成熟。我们之前证明，瘦素和脂多糖（LPS）可促进DCs表面共刺激分子的表达。经瘦素/LPS处理的DCs增强了小鼠针对4T1乳腺癌的T细胞反应。因此，在本研究中，我们在乳腺癌小鼠模型中研究了经瘦素和LPS处理的DC疫苗对参与肿瘤转移、血管生成及相关细胞因子的基因的影响。通过将4T1细胞皮下注射到同基因小鼠体内诱导肿瘤形成。在第12天和第19天，各小鼠组接受经瘦素处理的DC疫苗以及瘦素与LPS联合处理的疫苗。在第26天处死小鼠后，使用ELISA技术检测血清中IL-6和IL-33的水平，并通过实时PCR测量肿瘤中VEGF、CCL2、MMP9和CCL5基因的表达水平。与未处理的荷瘤小鼠相比，经瘦素处理的成熟DC（mDC）组中MMP9（0.33倍，p = 0.01）和CCL5（0.81倍，p = 0.02）的表达显著降低。经瘦素-LPS处理的mDC组中，参与转移和肿瘤生长的基因表达降低，包括VEGF（0.72倍，p = 0.03）、MMP9（0.26倍，p = 0.001）和CCL5（0.3倍，p = 0.006），表明对转移的预防更有效。两个处理组中CCL2基因的表达水平均呈轻微下降趋势，但这些变化无统计学意义。经瘦素处理的mDC组使IL-6的产生减少约16%（p = 0.02），而经瘦素-LPS处理的mDC组显著降低IL-6的产生约22%（p = 0.01），并使IL-33的产生增加约42%（p = 0.03）。本研究结果表明，经瘦素-LPS处理的mDC疫苗组降低了参与转移和血管生成的基因及细胞因子的表达，与经瘦素处理的mDC疫苗组相比显示出更高的疗效。
