Functional expression of TLR9 is associated to the metastatic potential of human lung cancer cell: functional active role of TLR9 on tumor metastasis. | LitMetric
Department of Respiratory Medicine, East Hospital, Tongji University, Shanghai, China.
Published: November 2007
AI Article Synopsis
Article Abstract
CpG-oligonucleotides (CpG-ODN), which induce signaling through Toll-like receptor 9 (TLR9), are widely used as adjuvants in therapy against cancer. However, tumor cells express functional TLR9 were recently reported and the immune effect of CpG ODN on tumor cells remains unclear. Here we investigated the direct effects of CpG ODN on human tumor cell line 95D cells using flow cytometric analysis and Western blotting. We found strongly high expression of TLR9 in 95D cells. Stimulation of 95D cells with CpG ODN induced significantly elevated secretion of IL-1alpha and IL-8, as well as the expression of CXCR4, ICAM-1 and MMP-2. Furthermore, the invasion of 95D cells and TLR9 modifying 95C cells were significantly enhanced by stimulation of CpG ODN, which could be abrogated by inhibitory CpG ODN and chloroquine. These results suggest that functionally active TLR9 is expressed on human tumor cell lines, and may represent a novel insight on the role of TIL9 agonist used in tumor immunotherapy.
State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
B lymphocytes have emerged as an important immune-regulating target. Inoculation with tumor cell membrane-derived vaccines is a promising strategy to activate B cells, yet their efficiency is limited due to lack of costimulatory molecules. To amplify B cell responses against tumor, herein, a spatiotemporally-synchronized antigen-adjuvant integrated nanovaccine, termed as CM-CpG-aCD40, is constructed by conjugating the immune stimulative CpG oligonucleotide and the anti-CD40 antibody (aCD40) onto the membrane vesicles derived from triple negative breast cancer cells.
Excessive inflammatory responses to viral infections, known as cytokine storms, are caused by overactivation of endolysosomal Toll-like receptors (TLRs) (TLR3, TLR7, TLR8, and TLR9) and can be lethal, but no specific treatment is available. Some quinoline derivatives with antiviral activity were tried during the recent coronavirus disease 2019 (COVID-19) pandemic, but showed serious toxicity, and their efficacy for treating viral cytokine storms was not established. Here, in order to discover a low-toxicity quinoline derivative as a candidate for controlling virally induced inflammation, we synthesized a series of derivatives of amodiaquine (ADQ), a quinoline approved as an antimalarial, and tested their effects on TLRs-mediated production of inflammatory cytokines and cell viability in vitro.
Leishmaniasis is amongst one of the most neglected tropical disease, caused by an intracellular protozoan of genus Leishmania. Currently, the most promising strategy to combat leishmaniasis, relies on chemotherapy but the toxicity and increasing resistance of the standard drugs, presses the demand for new alternatives. Immunization is arguably the best strategy for cure because an individual once infected becomes immune to the disease.
Paclitaxel is a widely used chemotherapeutic agent for treating various solid tumors. However, resulting neuropathic pain, often a lifelong side effect of paclitaxel, can limit dosing and compromise optimal treatment. The choroid plexus, located in the brain ventricles, spreads peripheral inflammatory reactions into the brain.
Unmethylated cytosine-phosphate-guanine (CpG) motifs are often found in bacteria and viruses, but are rare in mammals. In mammals, CpG oligodeoxynucleotides (CpG ODN) stimulate the innate immune system via toll-like receptor 9 (TLR9). However, TLR9 is absent in birds; instead, TLR21 serves as the receptor for CpG ODN.
