Neoadjuvant nivolumab plus bevacizumab therapy improves the prognosis of triple-negative breast cancer in humanized mouse models.

Abstract

The combination of immune checkpoint inhibitors and anti-angiogenic agents has been proposed as a promising strategy to improve the outcome of advanced triple-negative breast cancer (TNBC). However, further investigation is warranted to elucidate the specific mechanisms underlying the effects of combination therapy and its potential as neoadjuvant therapy for early-stage TNBC. In this study, we constructed humanized mouse models by engrafting the human immune system into severely immunodeficient mice and subsequently implanting TNBC cells into the model. The mice were treated with neoadjuvant combination therapy (bevacizumab combined with nivolumab), followed by in vivo imaging system to assess tumor recurrence and metastasis after surgery. The immune microenvironment of tumors was analyzed to investigate the potential mechanisms. Furthermore, we verified the impact of extending the interval before surgery or administering adjuvant therapy after neoadjuvant therapy on the prognosis of mice. Neoadjuvant combination therapy significantly inhibited tumor growth, prevented recurrence and metastasis by normalizing tumor vessels and inducing robust CD8+ T cell infiltration and activation in primary tumors (p < 0.001). In vivo experiments demonstrated that prolonging the interval before surgery or administering adjuvant therapy after neoadjuvant therapy did not enhance its efficacy. The preclinical study has demonstrated the therapeutic efficacy and mechanism of neoadjuvant combination therapy (nivolumab plus bevacizumab) in treating early TNBC.