VEGF165b augments NK92 cytolytic activity against human K562 leukemia cells by upregulating the levels of perforin and granzyme B via the VEGR1-PLC pathway

• Published in: Molecular immunology 2020-12, Vol.128, p.41-46
• Main Authors: Wang, Xiaoyin, Liang, Chen, Xia, Wenjiao, Guo, Changjiang, Niu, Zhiyuan, Zhu, Wuling, Zhang, Huiyong
• Format: Article
• Language: English
• Subjects: Angiogenesis Inhibitors - pharmacology; Cell Death - drug effects; Cell Death - physiology; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Proliferation - physiology; Cytolytic activity; Granzymes - metabolism; Human K562 leukemia cells; Humans; K562 Cells; Leukemia - drug therapy; Leukemia - metabolism; Neovascularization, Pathologic - metabolism; NK92; Perforin - metabolism; Signal Transduction - drug effects; Signal Transduction - physiology; Tumor Microenvironment - drug effects; Tumor Microenvironment - physiology; Up-Regulation - drug effects; Up-Regulation - physiology; Vascular Endothelial Growth Factor A - metabolism; Vascular Endothelial Growth Factor Receptor-1 - metabolism; VEGF165b; VEGFR1
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/j.molimm.2020.09.004

•VEGF165b treatment augments the cytolytic ability of NK92 against tumor cells in vitro.•VEGF165b treatment upregulates perforin and granzyme B.•3.VEGF165b activity is mediated by the VEGFR1-PLC pathway. Pro-angiogenic Vascular endothelial growth factors (VEGFs) exert immunosuppressive functions on some immune cells by interacting with VEGF receptors. Blocking the VEGF/VEGFR pathway could reverse the tumor immunosuppressive microenvironment to some degree. We recently demonstrated that the anti-angiogenic VEGF isoform VEGF165b, similar to other anti-angiogenic agents, inhibit the accumulation immunosuppressive cells such as Tregs and MDSCs. However, whether VEGF165b affects the functions of immune effector cells remain unclear. Here, NK92 cell line was utilized as an immune effector cell model. Our results verified that NK92 cells endogenously express VEGF165 and VEGFR1. Further investigation showed that NK92 treatment with VEGF165b augments its killing ability against human K562 leukemia cells by upregulating perforin and granzyme B through the VEGFR1-PLC pathway, whereas VEGF165b had no impact on the proliferation of NK92 cells in vitro. The results of this study improve our understanding of the immunomodulatory function of VEGF165b, which may help in enhancing the efficacy of NK92-based cancer immunotherapy.