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Remodels the Immunosuppressive Tumor Microenvironment by Combination of Bacillus Calmette–Guérin and Anti-PD-L1 in an Orthotopic Triple-Negative Breast Cancer Mouse Model

Authors Lu Y, Huang X, Liu X, He Y, Hu Z, Xu JW, Cao G, He W

Received 26 November 2020

Accepted for publication 3 March 2021

Published 30 March 2021 Volume 2021:14 Pages 2247—2258

DOI https://doi.org/10.2147/OTT.S294129

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Sanjay Singh


Yuan Lu, 1, 2 Xin Huang, 1, 2 Xiaoke Liu, 1, 2 Yu He, 1, 2 Zhe Hu, 1 Weize Xu, 1, 2 Gang Cao, 1– 3 Wenbo He 1, 2

1State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, 430070, People’s Republic of China; 2College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People’s Republic of China; 3College of Biomedicine and Health, Huazhong Agricultural University, Wuhan, 430070, People’s Republic of China

Correspondence: Wenbo He
College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People’s Republic of China
Tel +86 15337203990
Email [email protected]

Background: Targeting immunosuppressive tumor microenvironment (TME) is one of the important therapeutic strategies for triple-negative breast cancer (TNBC). The application of Bacillus Calmette–Guérin (BCG) in the clinical treatment of bladder cancer has shown that BCG is a strong inducer of immune activation and can remodel the immunosuppressive state of the TME. Meanwhile, previous studies have demonstrated that the 4T1 TNBC mouse model does not respond to anti-PD-L1 treatment alone. Therefore, it is necessary to explore the effect of BCG on TNBC, as well as the potential efficacy of BCG combined with anti-PD-L1.
Materials and Methods: In this study, we studied the effects of BCG treatment on the lymphocytes and transcriptome in the TME of an orthotopic TNBC mouse model, and evaluated the efficacy of combination therapy with BCG and anti-PD-L1 on the tumor.
Results: We found that three-dose BCG treatment could significantly inhibit tumor growth, while the single-dose BCG treatment was able to up-regulate the expression of chemokine-related genes and anti-tumor effect genes, down-regulate the expression of immunosuppressive-related genes, and increase tumor-infiltrating lymphocytes. The combination therapy of BCG and anti-PD-L1 has produced a marked oncolytic effect.
Conclusion: These findings emphasize that BCG treatment can relieve the immunosuppressive state of the TME, and indicate that the combination therapy of BCG and anti-PD-L1may be an efficacious treatment measure for TNBC.

Keywords: TME, BCG, PD-L1, TNBC, immunotherapy, combination therapy

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