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Polyinosinic-cytidylic acid as an adjuvant on natural killer- and dendritic cell-mediated antitumor activities

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Tumor Biology

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.

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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

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Acknowledgments

The clinical blood samples were provided by assistant professor Yang Nong of Hunan Provincial Tumor Hospital. This work was supported by the project sponsored by the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry (20111568 to FQ) and Doctoral Fund (20070533036) of the Ministry of Education of China (to FQ).

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Authors and Affiliations

  1. Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China

    Yu-Kun Huang

  2. Xiangya Third Hospital, Central South University, Changsha, 410013, People’s Republic of China

    Zhi Zheng

  3. Department of General Surgery, Xiangya Third Hospital, Central South University, Changsha, 410013, People’s Republic of China

    Fu Qiu

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  1. Yu-Kun Huang
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  2. Zhi Zheng
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  3. Fu Qiu
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Correspondence to Fu Qiu.

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Huang, YK., Zheng, Z. & Qiu, F. Polyinosinic-cytidylic acid as an adjuvant on natural killer- and dendritic cell-mediated antitumor activities. Tumor Biol. 34, 1615–1623 (2013). https://doi.org/10.1007/s13277-013-0693-3

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  • DOI: https://doi.org/10.1007/s13277-013-0693-3

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