Tumor Vasculature as an Emerging Pharmacological Target to Promote Anti-Tumor Immunity

• Published in: International journal of molecular sciences Vol. 24; no. 5; p. 4422
• Main Authors: Tzeng, Hong-Tai, Huang, Yu-Jie
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 23.02.2023; MDPI
• Subjects: Acidosis; Angiogenesis; Angiogenesis Inhibitors - therapeutic use; Antiangiogenics; Blood vessels; Breast cancer; Cytotoxicity; Endothelial cells; Endothelial Cells - pathology; endothelial heterogeneity; Heterogeneity; Humans; Hypoxia; Immune checkpoint; Immune response; Immune system; Immunotherapy; Kinases; Ligands; Lymphocytes; Melanoma; Metabolism; Metabolites; Metastasis; Molecular modelling; Neoplasms - pathology; Neovascularization, Pathologic - pathology; Neutrophils; Permeability; Pharmacology; Physiology; Review; Signal transduction; T cell receptors; tumor angiogenesis; Tumor Microenvironment; Tumors; Vascular endothelial growth factor; vasculature normalization; endothelial heterogeneity; vasculature normalization; immune response; immunotherapy; tumor angiogenesis
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24054422

Tumor vasculature abnormality creates a microenvironment that is not suitable for anti-tumor immune response and thereby induces resistance to immunotherapy. Remodeling of dysfunctional tumor blood vessels by anti-angiogenic approaches, known as vascular normalization, reshapes the tumor microenvironment toward an immune-favorable one and improves the effectiveness of immunotherapy. The tumor vasculature serves as a potential pharmacological target with the capacity of promoting an anti-tumor immune response. In this review, the molecular mechanisms involved in tumor vascular microenvironment-modulated immune reactions are summarized. In addition, the evidence of pre-clinical and clinical studies for the combined targeting of pro-angiogenic signaling and immune checkpoint molecules with therapeutic potential are highlighted. The heterogeneity of endothelial cells in tumors that regulate tissue-specific immune responses is also discussed. The crosstalk between tumor endothelial cells and immune cells in individual tissues is postulated to have a unique molecular signature and may be considered as a potential target for the development of new immunotherapeutic approaches.