Evolution of vascular normalization strategies: from anti-angiogenesis to remodeling the tumor microenvironment
Abstract
Although anti-angiogenic therapy has been widely used in the treatment of solid tumors, angiogenesis inhibition alone frequently induces acquired resistance and exacerbates tumor hypoxia, paradoxically promoting tumor progression. The concept of tumor vascular normalization has offered a new perspective to address this dilemma, shifting the therapeutic strategy from “vessel destruction” to “vessel repair.” This review systematically elucidates the pathological characteristics of aberrant tumor vasculature and the cascading responses driven by these abnormalities. We summarize the molecular regulatory networks underlying vascular normalization across multiple dimensions, including VEGF signaling, hypoxia-inducible factors, extracellular matrix remodeling, metabolic reprogramming, and immune cell coordination. On this basis, this review further explores how vascular normalization systematically reshapes the tumor immune microenvironment by alleviating immunosuppression, promoting T cell infiltration, supporting an IFN-γ-mediated positive feedback loop, and coordinating with tertiary lymphoid structure formation. Finally, we dissect the multicellular interaction networks among tumor cells, endothelial cells, pericytes, and immune cells, and propose future directions including the vascular-immune dual-biomarker system and the targeting of pericyte phenotypic switching. This review provides a systematic framework for understanding the synergistic mechanisms linking vascular normalization and immune reprogramming, and lays a foundation for optimizing combination therapeutic strategies.
Related
- Oncolytic reovirus: tumor-microenvironment remodeling, engineering constraints, and translational strategies
- Remodeling of the brain immune microenvironment in Alzheimer’s disease: interactions among microglia, astrocytes, complement, and the neurovascular unit
- Tumor cell-intrinsic mtDNA instability drives cGAS-dependent temporal remodeling of the melanoma immune microenvironment
- Oral artificial microbio-vaccine triggers synergistic immunogenic cell death induction and tumor microenvironment remodeling for liver cancer therapy.
- Metallostasis remodeling in rheumatoid arthritis: focus on iron, copper, and zinc in the synovial microenvironment
BibTeX
@article{huang2026evolution,
title = {{Evolution of vascular normalization strategies: from anti-angiogenesis to remodeling the tumor microenvironment}},
author = {Qian Huang and Yujing Guo and Sha Yin and Lunbiao Gan and Zehua Liu and Wenxiu Ru and Yu Lu and Sijia Di and Fengze Nie and Siyu Yao and Huanhuan Wan and Le Liu and Jiaqi Ning and Fa Yang and Weijun Qin and Weihong Wen},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1959437},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1959437},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Evolution of vascular normalization strategies: from anti-angiogenesis to remodeling the tumor microenvironment
AU - Qian Huang
AU - Yujing Guo
AU - Sha Yin
AU - Lunbiao Gan
AU - Zehua Liu
AU - Wenxiu Ru
AU - Yu Lu
AU - Sijia Di
AU - Fengze Nie
AU - Siyu Yao
AU - Huanhuan Wan
AU - Le Liu
AU - Jiaqi Ning
AU - Fa Yang
AU - Weijun Qin
AU - Weihong Wen
PY - 2026
DA - 2026/10/30
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1959437
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1959437
AB - Although anti-angiogenic therapy has been widely used in the treatment of solid tumors, angiogenesis inhibition alone frequently induces acquired resistance and exacerbates tumor hypoxia, paradoxically promoting tumor progression. The concept of tumor vascular normalization has offered a new perspective to address this dilemma, shifting the therapeutic strategy from “vessel destruction” to “vessel repair.” This review systematically elucidates the pathological characteristics of aberrant tumor vasculature and the cascading responses driven by these abnormalities. We summarize the molecular regulatory networks underlying vascular normalization across multiple dimensions, including VEGF signaling, hypoxia-inducible factors, extracellular matrix remodeling, metabolic reprogramming, and immune cell coordination. On this basis, this review further explores how vascular normalization systematically reshapes the tumor immune microenvironment by alleviating immunosuppression, promoting T cell infiltration, supporting an IFN-γ-mediated positive feedback loop, and coordinating with tertiary lymphoid structure formation. Finally, we dissect the multicellular interaction networks among tumor cells, endothelial cells, pericytes, and immune cells, and propose future directions including the vascular-immune dual-biomarker system and the targeting of pericyte phenotypic switching. This review provides a systematic framework for understanding the synergistic mechanisms linking vascular normalization and immune reprogramming, and lays a foundation for optimizing combination therapeutic strategies.
SN - 1664-3224
ER -