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ID 117305
Author
Kondoh, Kensuke Tokushima University
Nguyen, Na Thi Tokushima University
Afroj, Tania Tokushima University
Otsuka, Kenji Tokushima University
Nokihara, Hiroshi Tokushima University
Keywords
angiogenesis
biomarker
CXCL10/11
immune checkpoint inhibitor
lung cancer
Content Type
Journal Article
Description
Immune checkpoint inhibitor (ICI) programmed death (PD)-1/PD-ligand 1 (PD-L1) blockade has been approved for various cancers. However, the underlying antitumor mechanisms mediated by ICIs and the predictive biomarkers remain unclear. We report the effects of anti-PD-L1/PD-1 Ab in tumor angiogenesis. In syngeneic mouse models, anti-PD-L1 Ab inhibited tumor angiogenesis and induces net-like hypoxia only in ICI-sensitive cell lines. In tumor tissue and serum of ICI-sensitive cell line-bearing mice, interferon-γ (IFN-γ) inducible angiostatic chemokines CXCL10/11 were upregulated by PD-L1 blockade. In vitro, CXCL10/11 gene upregulation by IFN-γ stimulation in tumor cell lines correlated with the sensitivity of PD-L1 blockade. The CXCL10/11 receptor CXCR3-neutralizing Ab or CXCL11 silencing in tumor cells inhibited the antiangiogenic effect of PD-L1 blockade in vivo. In pretreatment serum of lung carcinoma patients receiving anti-PD-1 Ab, the concentration of CXCL10/11 significantly correlated with the clinical outcome. Our results indicate the antiangiogenic function of PD-1/PD-L1 blockade and identify tumor-derived CXCL10/11 as a potential circulating biomarker of therapeutic sensitivity.
Journal Title
Cancer Science
ISSN
13497006
Publisher
Japanese Cancer Association|John Wiley & Sons
Volume
112
Issue
12
Start Page
4853
End Page
4866
Published Date
2021-10-10
Rights
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
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DOI (Published Version)
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language
eng
TextVersion
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departments
Medical Sciences
University Hospital