Department of Immunology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Molecular Medicine Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
Department of Immunology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Molecular Medicine Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Department of Immunology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
Adv Med Sci. 2022 Mar;67(1):170-178. doi: 10.1016/j.advms.2022.02.006. Epub 2022 Mar 12.
The immunosuppressive microenvironment of tumors reduces the effectiveness of immunotherapies. Apelin as an immunosuppressor peptide is expressed in the microenvironment of many tumors. Thus, inhibition of apelin-related protumor activities can promote the effectiveness of cancer immunotherapy. Here, we investigated the efficacy of a dendritic cell (DC) vaccine in combination with an apelin receptor antagonist, ML221, to modulate Th1 and Th2 cell-related responses in breast cancer-bearing mice.
Tumor was induced in female BALB/c mice by injecting 7 × 10 4T1 cells in the right flank. Tumor-bearing mice were then given PBS, ML221, DC vaccine and "ML221 + DC vaccine" for 21 days. On day 37, mice were sacrificed and the frequency of Th1/Th2 cells in spleen and serum levels of IFN-γ/IL-10 were determined using flow cytometry and ELISA, respectively. Lung metastasis was evaluated in lung tissues stained with hematoxylin and eosin. Finally, the obtained data were analyzed using appropriate statistical tests.
Combination therapy with ML221 + DC vaccination was more effective in reducing tumor growth (P < 0.0001), preventing lung metastasis (P < 0.0001) and increasing survival rate (P < 0.01) compared to the control group. Moreover, combination treatment substantially increased the frequency of Th1 cells while decreasing the frequency of Th2 cells in the spleen compared to the control group (P < 0.01). It also reduced serum levels of IL-10 compared with the control group (P < 0.05).
Our findings showed that combination therapy using ML221 + DC vaccine can be considered as an effective cancer therapeutic program to potentiate anti-tumor immune responses.
肿瘤的免疫抑制微环境降低了免疫疗法的效果。阿皮林作为一种免疫抑制肽，在许多肿瘤的微环境中表达。因此，抑制阿皮林相关的促肿瘤活性可以促进癌症免疫治疗的效果。在这里，我们研究了树突状细胞（DC）疫苗联合阿皮林受体拮抗剂 ML221 对调节乳腺癌荷瘤小鼠 Th1 和 Th2 细胞相关反应的疗效。
通过在右侧肋部注射 7×10 4T1 细胞，在雌性 BALB/c 小鼠中诱导肿瘤。然后，给荷瘤小鼠注射 PBS、ML221、DC 疫苗和“ML221+DC 疫苗”，共 21 天。在第 37 天，处死小鼠，通过流式细胞术检测脾内 Th1/Th2 细胞的频率，ELISA 法检测血清 IFN-γ/IL-10 水平。用苏木精和伊红染色评估肺组织中的肺转移。最后，用适当的统计检验分析获得的数据。
与对照组相比，ML221+DC 疫苗联合治疗更有效地抑制肿瘤生长（P<0.0001），预防肺转移（P<0.0001），提高生存率（P<0.01）。此外，与对照组相比，联合治疗显著增加了脾内 Th1 细胞的频率，同时降低了 Th2 细胞的频率（P<0.01）。它还降低了与对照组相比的血清 IL-10 水平（P<0.05）。
我们的研究结果表明，ML221+DC 疫苗联合治疗可作为一种有效的癌症治疗方案，增强抗肿瘤免疫反应。
