Work

The vascular–immune interface in breast cancer: normalization strategies, combination therapy, and biomarkers

Year: 2026

Type: review

Abstract: Immune checkpoint inhibitors have improved outcomes in selected patients with breast cancer, particularly those with triple-negative disease, but most tumors remain refractory. Abnormal tumor vasculature is one contributor to this resistance. Disorganized, hyperpermeable vessels produce heterogeneous perfusion, hypoxia, acidosis, and elevated interstitial pressure; these changes impede drug delivery and lymphocyte trafficking while favoring regulatory T cells, myeloid-derived suppressor cells, and dysfunctional antigen presentation. Anti-angiogenic therapy can transiently reverse part of this phenotype. When dose and timing are appropriate, a vascular-normalization window improves perfusion and oxygenation, restores endothelial adhesiveness, and creates conditions in which chemotherapy and immune checkpoint blockade may work more effectively. This framework is biologically compelling, but clinical evidence in breast cancer remains uneven: activity has been reported in several early-phase combination studies, whereas large trials of bevacizumab-containing regimens have not consistently improved overall survival. Candidate biomarkers-including VEGF/VEGFR signaling, angiopoietin-Tie2 activity, PD-L1, high endothelial venules, tertiary lymphoid structures, circulating cytokines, and spatial patterns of immune exclusion-remain exploratory and are limited by assay variability and temporal heterogeneity. This narrative review examines the vascular - immune interface across breast cancer subtypes, distinguishes mechanistic rationale from clinical proof, and identifies priorities for biomarker-guided trials designed to define dose, sequence, and the normalization window.

Source: Frontiers in Oncology

DOI: 10.3389/fonc.2026.1962446

Authors: Yujing Zhang, Cai Yulan, Kaiguo Long, Qi Wang, Chuyu Liu, Feng Zeng

Institution: Zunyi Medical University

Language: English

Topic: Angiogenesis and VEGF in Cancer

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801