研究动态
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阿苯达唑诱导抗肿瘤效应并增强 PD-L1 阻断免疫疗法。

Albendazole induces an anti-tumor effect and potentiates PD-L1 blockade immunotherapy.

发表日期:2023 Sep 20
作者: Weinan Zhang, Zhiqiang He, Fucheng Liang, Jie Gong, Liuchang Tan, Juan Yang, Siji Song, Luoyingzi Xie, Yuangang Lu
来源: Parasites & Vectors

摘要:

以前,阿苯达唑(ABZ)被报道为一种抗寄生虫药物,而不是抗肿瘤药物。我们的研究旨在调查ABZ是否也具有潜在的抗肿瘤作用,通过塑造肿瘤免疫微环境,并探究ABZ是否可以与PD-L1阻断剂协同作用。我们在C57BL/6小鼠(C57)体内静脉注射B16F10荧光素(B16-luc)细胞,建立肺转移性黑色素瘤模型,并在皮下接种B16-luc细胞,建立皮下肿瘤模型。通过游标卡尺和体内成像测量小鼠的肿瘤体积和肿瘤转移部位。使用RNA测序分析肿瘤中免疫细胞的不同基因和通路。利用流式细胞术和免疫荧光分析浸润肿瘤的不同亚群的免疫细胞。结果显示,ABZ显著抑制肺黑色素瘤的转移,荧光强度和结节评分减少,并且调节皮下黑色素瘤的回归,肿瘤体积减少。此外,RNA测序结果显示,ABZ调节了肿瘤微环境中免疫细胞的基因表达水平和通路。与此同时,流式细胞术和免疫荧光显示,在ABZ治疗后,肿瘤中CD8+ T细胞、CD4+ T细胞和TH1细胞的数量和百分比增加。此外,ABZ与抗PD-L1治疗的联合应用在肺转移性和皮下黑色素瘤模型中显著增强了抗肿瘤疗效,并且相较于对照组,增加了CD8+ T细胞、CD4+ T细胞和TH1细胞的百分比。ABZ抑制黑色素瘤的生长和转移。此外,ABZ与PD-L1阻断剂协同作用介导肿瘤的回归。© 2023. 作者(们),在Springer-Verlag GmbH Germany的独家许可下,Springer Nature的一部分。
Previously, albendazole (ABZ) has been reported as an anti-parasitic drug rather than anti-tumor drug. Our study aim to investigate whether ABZ also has a potential anti-tumor effect by shaping the tumor immune microenvironment and interrogate whether ABZ could synergize with the PD-L1 blockade.C57BL/6 mice (C57) were intravenously injected with B16F10-luciferase (B16-luc) cells to establish a lung metastatic melanoma model and subcutaneously inoculated with B16-luc cells to establish a subcutaneous tumor model. The tumor volume and tumor metastasis loci of the mice were measured by a vernier caliper and in vivo imaging. RNA sequencing was performed to analyze the different genes and pathways of immune cells in the tumors. Flow cytometry and immunofluorescence were used to analyze the different subsets of tumor-infiltrating immune cells.The results suggested that ABZ significantly inhibited lung melanoma metastasis with decreased fluorescence intensity and nodule score and mediated the regression of subcutaneous melanoma in mice with decreased tumor volume. Moreover, RNA sequencing results showed that ABZ regulated the gene expression levels and pathways of immune cells in the tumor microenvironment (TME). Meanwhile, flow cytometry and immunofluorescence showed that the number and percentage of CD8+ T cells, CD4+ T cells, and TH1 cells were enhanced in tumors after ABZ treatment. Furthermore, the combination of ABZ and anti-PD-L1 treatment significantly potentiated anti-tumor efficacy in both lung metastasis and subcutaneous melanoma models and mediated an increase in the percentage of CD8+ T cells, CD4+ T cells, and TH1 cells as compared to the control group.ABZ inhibits melanoma growth and metastasis. Moreover, ABZ synergized with PD-L1 blockade mediates tumor regression.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.