title: Polyinosinic-cytidylic acid as an adjuvant on natural killer- and dendritic cell-mediated antitumor activities.
abstract: Previously, we demonstrated that treatment with E7(44-62) and the adjuvant polyinosinic-cytidylic acid (poly(I:C)) in a rodent model generates antitumor immune responses, but the effect of E7(44-62) with poly(I:C) on natural killer (NK)- and dendritic cell (DC)-mediated antitumor activities is still unclear. Our goal was to examine the antitumor effects of E7(44-62) with poly(I:C). We examined the ability of E7(44-62) with poly(I:C) to induce toll-like receptor 3 (TLR3) expression, tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) mRNA expression, and tumor cell-killing activity in human NK cells as well as its ability to induce CD11c and CD86 expression and proliferation in human DCs. We found that E7(44-62) with poly(I:C) treatment markedly increased TLR3 expression and cytotoxicity against HeLa cells in human NK92 cells. Moreover, treatment with E7(44-62) and poly(I:C) markedly up-regulated IFN-γ and TNF-α mRNA expression in NK92 cells. Human patients with cervical cancer exhibited a marked decrease in the frequency of DCs; however, ex vivo treatment with E7(44-62) and poly(I:C) restored DC frequency. Stimulation of human DCs in patients with E7(44-62) and poly(I:C) led to high levels of CD11c and CD86 expression. Our data reveal the involvement of E7(44-62) combined with poly(I:C) in potentiating antitumor cytotoxicity and cytokine-producing activities in human NK92 cells and DCs.
authors: Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.
authors: Yu-Kun
authors: YK
authors: Huang
authors: Zhi
authors: Z
authors: Zheng
authors: Fu
authors: F
authors: Qiu
mesh_terms: D000276:Adjuvants, Immunologic; D000328:Adult; D016022:Case-Control Studies; D002584:Cervix Uteri / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008875:Middle Aged; D011070:Poly I-C / Q000627:therapeutic use*; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D002578:Uterine Cervical Dysplasia / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D011070:Poly I-C