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http://ir.nhri.org.tw/handle/3990099045/14437
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| Title: | A Fc-VEGF chimeric fusion enhances PD-L1 immunotherapy via inducing immune reprogramming and infiltration in the immunosuppressive tumor microenvironment |
| Authors: | Kuo, CL;Chou, HY;Lien, HW;Yeh, CA;Wang, JR;Chen, CH;Fan, CC;Hsu, CP;Kao, TY;Ko, TM;Lee, AYL |
| Contributors: | National Institute of Cancer Research |
| 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-VEGF(121)-VEGF(165) (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-beta, 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. |
| Date: | 2023-02 |
| Relation: | Cancer Immunology Immunotherapy. 2023 Feb;72(2):351-369. |
| Link to: | http://dx.doi.org/10.1007/s00262-022-03255-9 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0340-7004&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000830951900001 |
| Cited Times(Scopus): | https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85138831873 |
| Appears in Collections: | [李岳倫] 期刊論文
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| ISI000830951900001.pdf | | 13229Kb | Adobe PDF | 180 | View/Open |
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