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Immunotherapies targeting tumor vasculature: challenges and opportunities
Abstract
Angiogenesis is a hallmark of cancer biology, and neoadjuvant therapies targeting either tumor vasculature or VEGF signaling have been developed to treat solid malignant tumors. However, these therapies induce complete vascular depletion leading to hypoxic niche, drug resistance, and tumor recurrence rate or leading to impaired delivery of chemo drugs and immune cell infiltration at the tumor site. Achieving a balance between oxygenation and tumor growth inhibition requires determining vascular normalization after treatment with a low dose of antiangiogenic agents. However, monotherapy within the approved antiangiogenic agents’ benefits only some tumors and their efficacy improvement could be achieved using immunotherapy and emerging nanocarriers as a clinical tool to optimize subsequent therapeutic regimens and reduce the need for a high dosage of chemo agents. More importantly, combined immunotherapies and nano-based delivery systems can prolong the normalization window while providing the advantages to address the current treatment challenges within antiangiogenic agents. This review summarizes the approved therapies targeting tumor angiogenesis, highlights the challenges and limitations of current therapies, and discusses how vascular normalization, immunotherapies, and nanomedicine could introduce the theranostic potentials to improve tumor management in future clinical settings.
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“Beyond these specific formulations, multiple studies have shown that partial vascular pruning and pericyte reinforcement, achieved with diverse TKIs, antibodies, and genetic modulators, can similarly normalize perfusion and enhance nanomedicine delivery across a range of tumor models [54, 55].”
From Overcoming tumor microenvironment barriers: transformable and bioinspired nanomedicine strategies for deep tumor penetration (2026) · cites this paper as [55]
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“, immature dendritic cells (DCs), regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAM)], and stromal cells also secrete the various cytokines and proangiogenic factors that support tumor angiogenesis (3).”
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Sheng, J., Yuan, W., Zhang, M., Chen, Z., Qi, Y., Zhao, Y., & Zhang, S. (2026) · Journal of Nanobiotechnology · doi:10.1186/s12951-026-04028-7 · Cited by 35
Metadata
- Authors
- Dianat-Moghadam, H., Nedaeinia, R., Keshavarz, M., Azizi, M., Kazemi, M., & Salehi, R.
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2023-09-01
- Volume
- 14
- ISSN
- 1664-3224
- PMC
- PMC10506263
- Cited by
- 36
- References
- 9
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