Polyinosinic-cytidylic acid as an adjuvant on natural killer- and dendritic cell-mediated antitumor activities
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RESEARCH ARTICLE
Polyinosinic-cytidylic acid as an adjuvant on natural killer- and dendritic cell-mediated antitumor activities Yu-Kun Huang & Zhi Zheng & Fu Qiu
Received: 13 December 2012 / Accepted: 3 February 2013 / Published online: 22 February 2013 # International Society of Oncology and BioMarkers (ISOBM) 2013
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 upregulated 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)
Y.-K. Huang Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha 410008, People’s Republic of China Z. Zheng Xiangya Third Hospital, Central South University, Changsha 410013, People’s Republic of China F. Qiu (*) Department of General Surgery, Xiangya Third Hospital, Central South University, Changsha 410013, People’s Republic of China e-mail: [email protected]
in potentiating antitumor cytotoxicity and cytokine-producing activities in human NK92 cells and DCs. Keywords Polyinosinic-cytidylic acid . Early gene . Natural killer cell . Dendritic cell . Antitumor activity Abbreviations poly(I:C) Polyinosinic-cytidylic acid NK Natural killer DC Dendritic cell TLR3 Toll-like receptor 3 TNF-α Tumor necrosis factor-alpha IFN-γ Interferon-gamma
Introduction Etiologically, human papillomavirus (HPV) infection is responsible for over 95 % of cervical cancers, and HPV-associated antigens are recognized by the host immune system. However, most HPV-associated antigens still have limited clinical use in the treatment of cervical cancer or precancerous lesions such as cervical intraepithelial neoplasia. It is generally accepted that expression of the early genes E6 and E7 is associated with HPV tumorigenicity and that E6 and E7 are tumor-specific antigen candidates for the development of a cervical cancer-specific vaccine. Previously, we reported that treatment with E7(44–62
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