Table 5 Other potential targets for TLR-based antitumor GBM treatment
From: Toll-like receptors and toll-like receptor-targeted immunotherapy against glioma
Potential antitumor agent | Definition | TLR target | In vitro cell line(s) | In vivo model(s) | Effects and mechanisms | Ref |
|---|---|---|---|---|---|---|
Zoledronic acid | Bisphosphonate that exhibits anticancer activity | TLR2 | U87 | n/a | Induced GBM cell apoptosis through overexpression of TLR2, interferon regulatory factor 5, and endoplasmic reticulum-nuclei-1 | [201] |
Ortho vanillin | An isomer of food supplement vanillin | TLR2 | GL261 and primary microglial cells derived from C57Bl/6 mice | n/a | Suppressed glioma-induced TLR2 signaling and cell proliferation in GAM through suppression of MMPs, IL-6, and iNOS | [75] |
Annexin A2 | Phospholipid-binding proteins that regulate membrane organization | TLR2 | GL261 | Murine GL261 implanted C57BL/6 mouse model | Enhanced antigen-specific T-cell responses via TLR2 activation. Fusing Annexin A2 with TLR agonist may induce synergetic antitumor immunity | [202] |
Cannabinoids | Compounds that function in inflammation and tumor progression | TLR2 | U87 | n/a | Inhibited PGN-induced TLR2-mediated NF-κB activation and tumor cell growth via CB1 cannabinoid receptor | [114] |
HMGB1 | Proinflammatory mediator released from dying tumor cells | TLR2 | GL26, GL261 | Murine GL261 implanted C57BL/6 mouse | Mediated TLR2-dependent glioma tumor regression associated with long-term survival in respond to Fms-like tyrosine kinase 3 ligand and thymidine kinase treatment | [84] |
TLR4 | A72, U87 | n/a | Contributed to immune evasion via antigen HLA-G regulation through interaction with TLR4 | [63] | ||
p62 | Signaling adaptor sequestosome-1 that shuttles ubiquitinated targets | TLR4 | T98G, primary GBM cells | Primary GBM G141119 glioma xenografts | Crucial for HMGB1-stimulated epithelial–mesenchymal transition and GBM cell invasion via TLR4-p38-Nrf2 activation | [162] |
HSP90α | Extracellular heat shock protein | TLR4 | U87 | n/a | Favored TLR4-mediated GBM cell migration | [155] |
Paeoniflorin | A polyphenol that exhibits anticancer activation | TLR4 | U87, U251, U87-luciferase | Human U87-implanted BALB/c nude mouse | Inhibited GBM growth through TLR4/Triad3A-axis-mediated TLR4 degradation | [204] |
Interferon regulatory factor 3 | A transcription factor that is critical to induce antiviral immune responses | TLR4 | U251, U87, SNB19 | n/a | Suppressed glioma progression and regulates the expression of glioma cytokine, chemokine, and miR155 via TLR4-mediated signaling | [203] |
Chloroquine | Inhibitor of endosomal maturation | TLR9 | D54MG | n/a | Inhibited CpG or non-CpG-ODN-induced tumor cell invasion through TLR signaling | [126] |