Zhang Weinan, He Zhiqiang, Liang Fucheng, Gong Jie, Tan Liuchang, Yang Juan, Song Siji, Xie Luoyingzi, Lu Yuangang
Department of Plastic and Cosmetic Surgery, Army Medical Center of PLA, Amy Medical University, No. 10, Daping Changjiang Branch Road, Yuzhong District, Chongqing, China.
Department of Plastic and Cosmetic Surgery, Chongqing Contemporary Plastic Surgery Hospital, Chongqing, China.
J Cancer Res Clin Oncol. 2023 Dec;149(18):16763-16778. doi: 10.1007/s00432-023-05415-5. Epub 2023 Sep 20.
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 T1 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 T1 cells as compared to the control group.
ABZ inhibits melanoma growth and metastasis. Moreover, ABZ synergized with PD-L1 blockade mediates tumor regression.
此前，阿苯达唑（ABZ）一直被报道为一种抗寄生虫药物而非抗肿瘤药物。我们的研究旨在探讨ABZ是否也具有通过塑造肿瘤免疫微环境发挥潜在抗肿瘤作用，并研究ABZ是否能与程序性死亡受体配体1（PD-L1）阻断剂协同作用。
将C57BL/6小鼠（C57）静脉注射B16F10荧光素酶（B16-luc）细胞以建立肺转移黑色素瘤模型，并皮下接种B16-luc细胞以建立皮下肿瘤模型。用游标卡尺和体内成像测量小鼠的肿瘤体积和肿瘤转移位点。进行RNA测序以分析肿瘤中免疫细胞的不同基因和通路。采用流式细胞术和免疫荧光分析肿瘤浸润免疫细胞的不同亚群。
结果表明，ABZ显著抑制肺黑色素瘤转移，荧光强度和结节评分降低，并介导小鼠皮下黑色素瘤消退，肿瘤体积减小。此外，RNA测序结果显示，ABZ调节肿瘤微环境（TME）中免疫细胞的基因表达水平和通路。同时，流式细胞术和免疫荧光显示，ABZ治疗后肿瘤中CD8 T细胞、CD4 T细胞和T1细胞的数量和百分比增加。此外，与对照组相比，ABZ与抗PD-L1治疗联合使用在肺转移和皮下黑色素瘤模型中均显著增强了抗肿瘤疗效，并介导了CD8 T细胞、CD4 T细胞和T1细胞百分比的增加。
ABZ抑制黑色素瘤生长和转移。此外，ABZ与PD-L1阻断剂协同作用介导肿瘤消退。
