肿瘤微环境是肿瘤恶性进程和药物产生耐受性的主要推动力，而微环境的改变与肿瘤血管的异常密切相关。血管正常化作为一种新型肿瘤治疗手段可以逆转异常的肿瘤血管结构和功能使之成为正常的血管系统，从而诱导肿瘤微环境内的免疫重塑。我们前期的研究发现丹参中的活性成分丹酚酸B联合免疫检查点抑制剂可以加强抗肿瘤作用，本课题主要通过探索丹酚酸B靶向肿瘤血管渗漏性实现血管正常化的可能性，进一步揭示其对免疫重塑过程中CD8+ T 细胞和中性粒细胞浸润的调节作用，尤其是对二者穿过内皮屏障方式的影响。此外，通过分析丹酚酸B对内皮连接关键分子VE-Cadherin及其介导的内皮稳定信号通路的作用，阐明其抑制肿瘤血管渗漏性的基础。最后，以内皮连接为中心，探究丹酚酸B能够促进CD8+ T 细胞跨内皮迁移的机理机制。以上研究将为丹酚酸B调节肿瘤“血管正常化-免疫重塑”反馈环作用提供科学依据并强化新型靶向血管治疗策略。

The tumor microenvironment is the major driver of tumor progression and resistance to anti-cancer drug. The alterations in the microenvironment are closely associated with abnormalities in tumor blood vessels. Vascular normalization as a novel therapy can reverse abnormal vascular structure and function back to normal vascular system, thereby inducing immune reprograming in the tumor microenvironment. Our previous study has demonstrated that Salvianolic acid B (SAB), the major active ingredient of Salvia miltiorrhiza, in combination with immune checkpoint inhibitor is able to enhance the anti-cancer effects. This project aims to investigate the possibility that SAB achieves vascular normalization via targeting tumor vascular permeability, and further to reveal the regulatory capability of SAB on the infiltration of CD8+ T cells and neutrophils in the process of immune reprograming, in particular their routes of passing through endothelial barrier. Furthermore, we are trying to uncover the basis of SAB on inhibiting vascular leak through analyzing its role in modulating the critical endothelial adhesion molecule, VE-Cadherin, and of which mediated signaling pathways involved in stabilizing endothelium. Lastly, the underlying mechanisms that SAB promotes the transcellular migration of CD8+ T cells will be accordingly explored with endothelial adhesion being focused. All of these studies will provide the scientific principle for the fact that SAB regulates “vascular normalization-immune reprograming” positive feedback loop and strengthen the novel vasculature-targeting strategies for cancer therapy.