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

Abstract

BackgroundTargeting 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 MethodsIn 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.ResultsWe 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.ConclusionThese 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.