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: Yu-Kun Huang, Zhi Zheng, Fu Qiu
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 34 Issue 3 Pg. 1615-23 (Jun 2013) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 23430582 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Cytokines
• TLR3 protein, human
• Toll-Like Receptor 3
• Poly I-C

Topics

• Adjuvants, Immunologic
• Adult
• Case-Control Studies
• Cervix Uteri (metabolism)
• Cytokines (metabolism)
• Dendritic Cells (immunology, metabolism)
• Enzyme-Linked Immunosorbent Assay
• Female
• Flow Cytometry
• Humans
• Killer Cells, Natural (immunology, metabolism)
• Middle Aged
• Poly I-C (therapeutic use)
• Toll-Like Receptor 3 (metabolism)
• Tumor Cells, Cultured
• Uterine Cervical Neoplasms (immunology, metabolism, prevention & control)
• Uterine Cervical Dysplasia (immunology, metabolism, prevention & control)