Abstract
Abstract
Background
Immunotherapy is an emerging cancer therapy with potential great success; however, immune checkpoint inhibitor (e.g., anti-PD-1) has response rates of only 10–30% in solid tumor because of the immunosuppressive tumor microenvironment (TME). This affliction can be solved by vascular normalization and TME reprogramming.
Methods
By using the single-cell RNA sequencing (scRNAseq) approach, we tried to find out the reprogramming mechanism that the Fc-VEGF chimeric antibody drug (Fc-VFD) enhances immune cell infiltration in the TME.
Results
In this work, we showed that Fc-VEGF121-VEGF165 (Fc-VEGF chimeric antibody drug, Fc-VFD) arrests excess angiogenesis and tumor growth through vascular normalization using in vitro and in vivo studies. The results confirmed that the treatment of Fc-VFD increases immune cell infiltration including cytotoxic T, NK, and M1-macrophages cells. Indeed, Fc-VFD inhibits Lon-induced M2 macrophages polarization that induces angiogenesis. Furthermore, Fc-VFD inhibits the secretion of VEGF-A, IL-6, TGF-β, or IL-10 from endothelial, cancer cells, and M2 macrophage, which reprograms immunosuppressive TME. Importantly, Fc-VFD enhances the synergistic effect on the combination immunotherapy with anti-PD-L1 in vivo.
Conclusions
In short, Fc-VFD fusion normalizes intratumor vasculature to reprogram the immunosuppressive TME and enhance cancer immunotherapy.
Funder
Ministry of Science and Technology, Taiwan
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology,Immunology,Immunology and Allergy
Cited by
4 articles.
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