Cancer Immunotherapy with "Vascular-Immune" Crosstalk as Entry Point: Associated Mechanisms, Therapeutic Drugs and Nano-Delivery Systems.

ABSTRACT

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.