Vascular normalization in immunotherapy: A promising mechanisms combined with radiotherapy

Abstract

Leakage and compression of blood vessels may result in deprivation of blood flow to a large number of tumor tissues, which can lead to tumor hypoxia. Hypoxia induces an increase in the expression of hypoxia-inducible factor 1 in tumor cells, which induces angiogenesis in tumors through the high expression of vascular endothelial growth factor, thereby forming a positive feedback vicious circle. Improving hypoxia by normalizing blood vessels and improving radiosensitivity by immunotherapy has emerged as a new application of combined immunotherapy and radiotherapy. Interferon γ produced by CD4 + /CD8 + T cells, induced by immune checkpoint inhibitors, plays an important role in the normalization of blood vessels; tumor-associated eosinophils also play a role in the process of immunotherapy-induced blood vessel normalization. In addition, the reduction in regulatory T cells induced by immune checkpoint inhibitors can increase eosinophil levels, which promotes the further development of vascular normalization mechanisms. This review focuses on the mechanism of immunotherapy to normalize blood vessels, and proposes a good prospect for improving hypoxia. Due to the narrow vascular normalization window of anti-angiogenesis therapy, discovery of the vascular normalization effect of immunotherapy provides a new idea for the combined application of immunotherapy and radiotherapy. The enlarged vascular normalization window and improved hypoxia provide a good opportunity for the subsequent implementation of radiotherapy. The above sorting and analysis may pave the way for a promising strategy for cancer treatment via combined immunotherapy and radiotherapy.

Keywords: Hypoxia; Immune checkpoint inhibitors; Immunotherapy; Radiotherapy; Vascular normalization.