Fig. 3
From: Toll-like receptors and toll-like receptor-targeted immunotherapy against glioma
Cross talk between immune cells and glioma via TLRs in glioma TME. Activation of TLR3, 7, 8, and 9 on microglia inhibits glioma growth via secretion of pro-inflammatory cytokines such as ILs, TNFs, and IFNs. Agonists initiate TLR7/9 functions on pDCs to stimulate NK and microglia through IFN secretion and diminish infiltrating Treg, while blockade of TLR7/9 accumulates Treg and accelerate glioma progression. Activation and expansion of cytotoxic T-cells are stimulated by pDC and TLR2/7 expressed on mDC to exhibit antitumor activity. The tumor-infiltrating microglia can be educated by glioma to transit into protumor phenotype (GAM) and promote glioma invasion and progression through release of MMPs, ILs, and iNOS. TLR2, 3, and 4 are necessary for GSC differentiation or development. GSC activates TLR4-expressing GAMs, which release IL-6 that further promotes GSC development, forming a positive loop to support glioma development. The green and red arrows represent promotion and inhibition, respectively