Vaccine-induced T-helper-1 and endocrine therapy in an estrogen receptor alpha low breast cancer model
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Abstract
The standard of care options for patients with triple negative breast cancer is limited to primarily surgery and chemotherapy. Recent evidence has demonstrated that combining immune therapeutic strategies with standard therapies increased efficacy in clinical trials and mouse models of breast cancer. Endocrine therapy, such as tamoxifen, has traditionally only been used to treat estrogen receptor positive breast cancer, but results of early tamoxifen clinical trials have revealed increased clinical activity in estrogen receptor-negative/low tumors. The goal of this study was to determine if combination immune therapy and endocrine therapy could inhibit tumor growth in an estrogen receptor-low mouse model. We observed that immunization targeting the tumor antigen insulin-like growth factor receptor-1 inhibited tumor growth dependent on interferon-gamma-secreting CD4+ T-cells. Interferon-gamma upregulated expression of the tumor suppressor phosphatase and tensin homolog in vitro. Vaccination induced sensitivity to treatment with either tamoxifen or anastrozole and the combination therapy was more effective than any single agent alone. Our study suggests that strategies incorporating antigen-specific type I T cells in conjunction with non-standard endocrine therapy regimens can improve outcomes in patients with triple negative breast cancer.
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