title: The antitumor effect of the toll-like receptor 3 ligand polyinosinic-cytidylic acid as an adjuvant.
abstract: Although polyinosinic-polycytidylic acid (poly(I:C)) has been applied in tumor immunity as a Toll-like receptor 3 (TLR3) ligand, the interaction between poly(I:C) and TLR3 is still unclear, as are the mechanisms underlying the antitumor effect of poly(I:C). Our aim was to investigate the interaction between poly(I:C) and TLR3, as well as the mechanisms underlying the antitumor effect of poly(I:C). NK92 cells were maintained in medium (untreated group), or medium containing E7(44-62) (E7 group) or E7(44-62)+poly(I:C) (poly(I:C)/E7 group), and we measured the expression of TLR3 mRNA, p-p65, and IκB-α protein. The cells were first incubated in medium alone or medium containing TLR3 monoclonal antibody, and then in medium containing poly(I:C)/E7. Finally, we measured the level of interferon-beta (INF-β) in the supernatant and determined the tumor cell-killing effect of the NK92 cells. At 1 h, the expression of TLR3 mRNA in the poly(I:C)/E7 group was markedly higher than that in the untreated and E7 groups (P < 0.05). When compared with the poly(I:C)/E7 group, the expression of IκB-α was dramatically increased in the E7 and untreated groups, and the expression of p-p65 was dramatically decreased in the E7 and untreated groups (all P < 0.05). At 24 h, INF-β content and tumor cell-killing activity in the poly(I:C)/E7 group were markedly higher than those in the untreated group (P < 0.001, <0.05, respectively). Treatment with TLR3 monoclonal antibody significantly inhibited poly(I:C)/E7-induced INF-β secretion and tumor cell-killing activity in NK92 cells (P < 0.001, <0.05, respectively). The interaction between poly(I:C) and TLR3 plays an important role in the antitumor immunity of NK92 cells. In addition, the interaction between poly(I:C) and TLR3 increases INF-β expression, which may be attributed to the activation of NFκB.
authors.affiliation: Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410078, Hunan Province, People's Republic of China.
authors.forename: Yu-Kun
authors.initials: YK
authors.lastname: Huang
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zheng
authors.forename: Chun-Xia
authors.initials: CX
authors.lastname: Cheng
authors.forename: Lu-Ying
authors.initials: LY
authors.lastname: Wang
authors.forename: Yue-Ran
authors.initials: YR
authors.lastname: Li
authors.forename: Fu
authors.initials: F
authors.lastname: Qiu
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000494:pharmacology; D002277:Carcinoma / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D005260:Female; D006367:HeLa Cells; D006801:Humans; D020672:I-kappa B Proteins / Q000096:biosynthesis; D007369:Interferon Inducers / Q000494:pharmacology*; D016899:Interferon-beta / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology; D008024:Ligands; D000072000:NF-KappaB Inhibitor alpha; D011070:Poly I-C / Q000494:pharmacology*; D051196:Toll-Like Receptor 3 / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D002583:Uterine Cervical Neoplasms / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D020672:I-kappa B Proteins; D007369:Interferon Inducers; D008024:Ligands; C000606204:NFKBIA protein, human; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D000072000:NF-KappaB Inhibitor alpha; D016899:Interferon-beta; D011070:Poly I-C