Tumor vasculature is characterized by aberrant structure and function, resulting in immune suppressive profiles of tumor microenvironment (TME) through limiting immune cell infiltration into
tumors. The defective vascular perfusion in
tumors also impairs the delivery and efficacy of chemotherapeutic agents. Targeting abnormal
tumor blood vessels has emerged as an effective therapeutic strategy to improve the outcome of
chemotherapy and
immunotherapy. In this study, we demonstrated that
Salvianolic acid B (SalB), one of the major ingredients of Salvia miltiorriza elicited vascular normalization in the mouse models of
breast cancer, contributing to improved delivery and response of chemotherapeutic agent
cisplatin as well as attenuated
metastasis. Moreover, SalB in combination with anti-PD-L1 blockade retarded
tumor growth, which was mainly due to elevated infiltration of immune effector cells and boosted delivery of anti-PD-L1 into
tumors. Mechanistically,
tumor cell
enhancer of zeste homolog 2 (Ezh2)-driven
cytokines disrupted the endothelial junctions with diminished
VE-cadherin expression, which could be rescued in the presence of SalB. The restored vascular integrity by SalB via modulating the interactions between
tumor cells and endothelial cells (ECs) offered a principal route for achieving vascular normalization. Taken together, our data elucidated that SalB enhanced sensitivity of
tumor cells to
chemotherapy and
immunotherapy through triggering
tumor vascular normalization, providing a potential therapeutic strategy of combining SalB and
chemotherapy or
immunotherapy for patients with
breast cancer.