From vascular normalization to VEGF-independent escape: multi-omics-defined angio-immune ecosystem states
Baolai Li1, Haitao Song1, Yongmei Dai1
1Department of Obstetrics, Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao, Shandong, China.
Frontiers in Cell and Developmental Biology
|July 23, 2026
Summary
Tumor resistance to anti-angiogenic therapy and immune checkpoint blockade involves complex angio-immune ecosystem states. Understanding these states is key to developing effective, long-term cancer treatments.
Area of Science:
- Oncology
- Immunology
- Cancer Biology
Background:
- Anti-angiogenic therapy and immune checkpoint blockade are crucial cancer treatments.
- Therapeutic benefits are often transient, suggesting resistance mechanisms.
- Resistance may stem from ecosystem-level tumor microenvironment reprogramming.
Purpose of the Study:
- To define and characterize angio-immune ecosystem states associated with therapeutic resistance.
- To identify specific configurations of vascular, immune, and spatial factors.
- To develop a framework for stratifying patients and tracking resistance longitudinally.
Main Methods:
- Integration of bulk transcriptional modules.
- Application of single-cell-anchored cell-state programs.
- Analysis of spatial neighborhood features.
Main Results:
- Identified four resistance-associated angio-immune ecosystem states.
- These states involve endothelial-stromal gatekeeping, limited normalization windows, hypoxia/myeloid-driven immunosuppression, and VEGF-independent perfusion escape.
- Linked resistance to specific spatial configurations within the tumor microenvironment.
Conclusions:
- Angio-immune ecosystem states provide a framework for understanding transient therapeutic benefits.
- This framework enables state-matched combination therapies.
- Linking resistance to spatial configurations can guide treatment strategies.
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