Neem Leaf Glycoprotein in Cancer Immunomodulation and Immunotherapy

Abstract

Abstract Neem (Azadirachta indica) is a well-known tree with immense medicinal properties and is the most versatile medicinal plant having a wide spectrum of biological activity. A group from Chittaranjan National Cancer Institute, Kolkata, India identified a glycoprotein in an aqueous preparation from neem leaves and it has several immunomodulatory functions, detrimental for tumor growth. The glycoprotein is designated as neem leaf glycoprotein or NLGP and preclinical studies established NLGP as a therapeutic tool for eradication and/or sustained restriction of murine tumor growth, based on several evidences in favor of possible multifaceted antitumor therapeutic benefits. First, NLGP rectifies immune evasion strategies that ultimately licenses better CD8+ T cell-mediated tumor killing. NLGP polarizes type 1 immune-microenvironment over regulatory-microenvironment. NLGP reduces frequency and suppressive properties of regulatory-immune cells (Tregs, myeloid-derived suppressor cells, tumor-associated macrophages) within tumor-microenvironment (TME). It also inhibits indoleamine 2,3-dioxygenase to maintain optimum tryptophan supply to T cells. As a vaccine adjuvant, it promotes central and effector memory cells in lymph node and spleen respectively to induce sustained tumor growth restriction. Besides, NLGP regulates hypoxia within TME and promotes vascular normalization by targeting hypoxia inducing factor 1-alpha-mediated vascular endothelial growth factor secretion. NLGP impedes the metastatic tumor growth in distant organs. A unique immunomodulation on host immune system by NLGP to restrain malignant growth definitely establishes NLGP as a candidate cancer drug.