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Cited by 688

The DOI matches its Crossref record; 99 of the 99 references it cites were found in a registry or an index.

Combination of anti-angiogenic therapy and immune checkpoint blockade normalizes vascular-immune crosstalk to potentiate cancer immunity

Open access
Lee, Won Suk, Yang, Hannah, Chon, Hong Jae, Kim, Chan·2020·Experimental & Molecular Medicine
DOI 10.1038/s12276-020-00500-y
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Abstract

Cancer immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized the treatment of advanced cancers. However, the tumor microenvironment (TME) functions as a formidable barrier that severely impairs the efficacy of ICIs. While the crosstalk between tumor vessels and immune cells determines the nature of anti-tumor immunity, it is skewed toward a destructive cycle in growing tumors. First, the disorganized tumor vessels hinder CD8+T cell trafficking into the TME, disable effector functions, and even kill T cells. Moreover, VEGF, the key driver of angiogenesis, interferes with the maturation of dendritic cells, thereby suppressing T cell priming, and VEGF also induces TOX-mediated exhaustion of CD8+T cells. Meanwhile, a variety of innate and adaptive immune cells contribute to the malformation of tumor vessels. Protumoral M2-like macrophages as well as T H 2 and Treg cells secrete pro-angiogenic factors that accelerate uncontrolled angiogenesis and promote vascular immaturity. While CD8+T and CD4+T H 1 cells suppress angiogenesis and induce vascular maturation by secreting IFN-γ, they are unable to infiltrate the TME due to malformed tumor vessels. These findings led to preclinical studies that demonstrated that simultaneous targeting of tumor vessels and immunity is a viable strategy to normalize aberrant vascular-immune crosstalk and potentiate cancer immunotherapy. Furthermore, this combination strategy has been evidently demonstrated through recent pivotal clinical trials, granted approval from FDA, and is now being used in patients with kidney, liver, lung, or uterine cancer. Overall, combining anti-angiogenic therapy and ICI is a valid therapeutic strategy that can enhance cancer immunity and will further expand the landscape of cancer treatment.

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Metadata

Authors
Lee, W. S., Yang, H., Chon, H. J., & Kim, C.
Venue
Experimental & Molecular Medicine
Publisher
Springer Science and Business Media LLC
Published
2020-09
Volume
52
Issue
9
Pages
1475-1485
ISSN
  • 1226-3613 (ISSN-L)
  • 2092-6413
DOI
10.1038/s12276-020-00500-y
OpenAlex
W3084409519
Cited by
688
References
99
FWCI
24.38
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: Combination of anti-angiogenic therapy and immune checkpoint blockade normalizes vascular-immune crosstalk to potentiate cancer immunity. https://app.cochat.ai/papers/10.1038/s12276-020-00500-y
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Lee, W. S., Yang, H., Chon, H. J., & Kim, C. (2020). Combination of anti-angiogenic therapy and immune checkpoint blockade normalizes vascular-immune crosstalk to potentiate cancer immunity. Experimental & Molecular Medicine. https://doi.org/10.1038/s12276-020-00500-y

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.