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Zhijie Jiang, Zhujun Fang, Dongsheng Hong, Xiaojuan Wang Department of Clinical Pharmacy, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, People’s Republic of ChinaCorrespondence: Xiaojuan Wang, Email xiaojuanwang1992@zju.edu.cnAbstract: Tumor vessels characterized by abnormal functions and structures hinder the infiltration and immune antigen presentation of immune cells by inducing the formation of an immunosuppressive microenvironment (“cold” environment). Vascular-targeted therapy has been proven to enhance immune stimulation and the effectiveness of immunotherapy by modulating the “cold” microenvironment, such as hypoxia and an acidic microenvironment. Notably, a therapeutic strategy based on “vascular-immune” crosstalk can achieve dual regulation of tumor vessels and the immune system by reprogramming the tumor microenvironment (TME), thus forming a positive feedback loop between tumor vessels and the immune microenvironment. From this perspective, we discuss the factors of tumor angiogenesis and “cold” TME formation. Building on this foundation, some vascular-targeted therapeutic drugs will be elaborated upon in detail to achieve dual regulation of tumor vessels and immunity. More importantly, we focus on cutting-edge nanotechnology in view of “vascular-immune” crosstalk and discuss the rational fabrication of tailor-made nanosystems for efficiently enhancing immunotherapy. Keywords: immunotherapy, nano-delivery systems, anti-angiogenic therapy, “vascular-immune” crosstalk, tumor vessels