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Moreover, the frequency of lethal\u2010RGS5\n                    <jats:sup>high<\/jats:sup>\n                    \u00a0pericytes within tumor was found to increase with disease progression, which signifies the presence of altered cell death pathway within tumor microenvironment\u00a0(TME). In this study, we checked whether and how neem leaf glycoprotein (NLGP)\u2010immunotherapy\u2010mediated tumor growth restriction is associated with modification of pericytes' signaling, functions and its interaction with ECs. Analysis of pericytes isolated from tumors of NLGP treated mice suggested that NLGP treatment promotes apoptosis of NG2\n                    <jats:sup>+<\/jats:sup>\n                    RGS5\n                    <jats:sup>high<\/jats:sup>\n                    \u2010fuctionally altered pericytes by downregulating intra\u2010tumoral TGF\u03b2,\u00a0along with maintenance of more matured RGS5\n                    <jats:sup>neg<\/jats:sup>\n                    \u00a0pericytes. NLGP\u2010mediated inhibition of TGF\u03b2 within TME rescues binding of RGS5 with G\u03b1i and thereby termination of PI3K\u2010AKT mediated survival signaling by downregulating Bcl2 and initiating pJNK mediated apoptosis. Limited availability of\u00a0TGF\u03b2\u00a0also prevents complex\u2010formation between RGS5 and Smad2 and rapid RGS5 nuclear translocation to mitigate alternate immunoregulatory functions of RGS5\n                    <jats:sup>high<\/jats:sup>\n                    \u00a0tumor\u2010pericytes. We also observed binding of Ang1 from pericytes with Tie2 on ECs in NLGP\u2010treated tumor, which support re\u2010association of pericytes with endothelium and subsequent vessel stabilization. Furthermore, NLGP\u2010therapy\u2010 associated\u00a0RGS5 deficiency relieved CD4\n                    <jats:sup>+<\/jats:sup>\n                    \u00a0and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells from anergy by regulating \u2018alternate\u2010APC\u2010like\u2019 immunomodulatory characters of tumor\u2010pericytes. Taken together, present study described the mechanisms of NLGP's effectiveness in normalizing tumor\u2010vasculature by chiefly modulating pericyte\u2010biology and EC\u2010pericyte interactions in tumor\u2010host to further strengthen its translational potential as single modality treatment.\n                  <\/jats:p>","DOI":"10.1096\/fj.202101093r","type":"journal-article","created":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T11:23:22Z","timestamp":1648812202000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["NLGP regulates RGS5\u2010TGF\u03b2 axis to promote pericyte\u2010dependent vascular normalization during restricted tumor growth"],"prefix":"10.1096","volume":"36","author":[{"given":"Shayani","family":"Dasgupta","sequence":"first","affiliation":[{"name":"Department of Immunoregulation and Immunodiagnostics Chittaranjan National Cancer Institute  Kolkata 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