Abstract
Background
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.
Methods
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.
Results
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.
Conclusion
ABZ inhibits melanoma growth and metastasis. Moreover, ABZ synergized with PD-L1 blockade mediates tumor regression.
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Data availability
All data used in this study are included in the article. Please contact the corresponding author for data requests.
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Acknowledgements
This work was supported by research grants from the National Natural Science Foundation of China (Nos.81672694, 82272763). The authors would like to thank Prof. Wenyue Xu for providing laboratory support.
Funding
This work was supported by research grants from the National Natural Science Foundation of China (Nos.81672694, 82272763).
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W.N.Z., Z.Q.H., L.Y.Z.X. and Y.G.L. designed experimental research. W.N.Z., Z.Q.H., L.Y.Z.X., J. G. and L.C.T completed experimental research. W.N.Z., Z.Q.H. and L.Y.Z.X. wrote the first draft of the paper, prepared all figures and completed all data analysis. W.N.Z. and F.C.L. completed draft of revision and experiments of revision. J. Y., S. J. S., L.Y.Z.X. and Y.G.L. reviewed manuscript. L.Y.Z.X. and Y.G.L. are the creator and person in charge of the entire project. All authors have read and agreed to the final text.
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The study protocol was approved by the Ethical Review of Experimental Animals of the Army Medical Center of the PLA (No. AMUWEC20237002).
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Zhang, W., He, Z., Liang, F. et al. Albendazole induces an anti-tumor effect and potentiates PD-L1 blockade immunotherapy. J Cancer Res Clin Oncol 149, 16763–16778 (2023). https://doi.org/10.1007/s00432-023-05415-5
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DOI: https://doi.org/10.1007/s00432-023-05415-5