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Updated: Oct 17, 2025
Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology
Published on: May 2, 2025
Programmed death (PD)-1/PD-ligand 1 blockade mediates antiangiogenic effects by tumor-derived CXCL10/11 as a
Atsushi Mitsuhashi1, Kensuke Kondoh1, Kazuki Horikawa2
1Department of Respiratory Medicine and Rheumatology, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.
Abstract:
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.
Insights
Immune checkpoint inhibitors (ICIs) block PD-1/PD-L1 to inhibit tumor growth by reducing blood vessel formation. Tumor-produced CXCL10/11 chemokines are key to this antiangiogenic effect and may predict treatment response.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Immune checkpoint inhibitors (ICIs) targeting programmed death (PD)-1/PD-ligand 1 (PD-L1) are effective cancer therapies.
- The precise antitumor mechanisms and predictive biomarkers for ICI efficacy remain incompletely understood.
Purpose of the Study:
- To investigate the impact of anti-PD-L1/PD-1 antibodies on tumor angiogenesis.
- To identify potential biomarkers associated with ICI response.
Main Methods:
- Utilized syngeneic mouse models and in vitro tumor cell line experiments.
- Analyzed tumor tissue and serum for chemokine expression (CXCL10/11) and receptor (CXCR3) interactions.
- Correlated chemokine levels with clinical outcomes in lung carcinoma patients treated with anti-PD-1 antibodies.
Main Results:
- Anti-PD-L1 antibodies inhibited tumor angiogenesis and induced hypoxia in ICI-sensitive models.
- PD-L1 blockade upregulated angiostatic chemokines CXCL10/11, dependent on interferon-γ (IFN-γ).
- CXCL10/11-CXCR3 axis disruption abrogated the antiangiogenic effect; CXCL10/11 serum levels correlated with patient outcomes.
Conclusions:
- PD-1/PD-L1 blockade exerts antiangiogenic effects.
- Tumor-derived CXCL10/11 is a critical mediator of ICI-induced antiangiogenesis.
- CXCL10/11 represents a potential circulating biomarker for predicting ICI therapeutic sensitivity.
