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On the other hand, the expression of <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content> receptors (<jats:styled-content style=\"fixed-case\">VEGFR<\/jats:styled-content>) in this cell lineage was also reported. Although the function of <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">VEGFR<\/jats:styled-content> axis plays a pivotal role in macrophages infiltration and angiogenesis, however, there is still lack of the direct evidence to show the role of <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content> as an autocrine operating in M2 macrophages, particularly for immunomodulation. In our study, we surprisingly discovered that M2 macrophages polarized by baicalin can simultaneously express <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content> and its receptors. Taking advantage of this unique culture system, we were able to investigate the biological activity of M2 macrophages in response to the autocrine <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content> milieu. Our results showed that the expression of programmed death\u2010ligand 1 (<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010L1) on M2 macrophages was significantly up\u2010regulated in autocrine <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content> milieu. Through the blockade of autocrine <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content> signalling, <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010L1 expression on M2 macrophages was dramatically down\u2010regulated. Furthermore, transplantation of <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u2010L1<jats:sup>+<\/jats:sup> M2 macrophage stimulated by autocrine <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content> into allogeneic mice significantly suppressed host <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup>\/<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8<jats:sup>+<\/jats:sup> T cells in the peripheral blood and increased <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup><jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>25<jats:sup>+<\/jats:sup> regulatory T cells in the bone marrow. In conclusion, our findings provide a novel biological basis to support the current successful strategy using combined <jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>\u20101 signalling blockade in cancer therapy.<\/jats:p>","DOI":"10.1111\/jcmm.14027","type":"journal-article","created":{"date-parts":[[2018,11,20]],"date-time":"2018-11-20T08:49:10Z","timestamp":1542703750000},"page":"1257-1267","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":118,"title":["Autocrine <scp>VEGF<\/scp> signalling on M2 macrophages regulates <scp>PD<\/scp>\u2010L1 expression for immunomodulation of T cells"],"prefix":"10.1111","volume":"23","author":[{"given":"Yin\u2010Siew","family":"Lai","sequence":"first","affiliation":[{"name":"Department of Biological Science and Technology National Pingtung University of Science and Technology Pingtung 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