Toll‑like receptor agonist rMBP‑NAP enhances antitumor cytokines production and CTL activity of peripheral blood mononuclear cells from patients with lung cancer

Ding,Cong; Li,Li; Zhang,Yi; Ji,Zhenyu; Zhang,Chenglong; Liang,Taotao; Guo,Xun; Liu,Xin; Kang,Qiaozhen

doi:10.3892/ol.2018.9182

Toll‑like receptor agonist rMBP‑NAP enhances antitumor cytokines production and CTL activity of peripheral blood mononuclear cells from patients with lung cancer

Authors:
- Cong Ding
- Li Li
- Yi Zhang
- Zhenyu Ji
- Chenglong Zhang
- Taotao Liang
- Xun Guo
- Xin Liu
- Qiaozhen Kang
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Affiliations: Department of Protein Function and Immunomodulatory Laboratory, School of Life Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China, Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
Published online on: July 20, 2018 https://doi.org/10.3892/ol.2018.9182
Pages: 4707-4712

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Abstract

Toll‑like receptor (TLR) agonists are known for their ability to inhibit tumor progression via enhancing antitumor cytokines production and cytotoxic T lymphocyte (CTL) activity. Recombinant Helicobacter pylori neutrophil‑activating protein fused with maltose‑binding protein (rMBP‑NAP) has been reported as a novel TLR agonist for antitumor treatment in murine models. The present study aimed to determine the potential and efficacy of the rMBP‑NAP for antitumor treatment prior to further clinical trials. The rMBP‑NAP was expressed and purified for subsequent experiments. Peripheral blood mononuclear cells (PBMCs) from health donors and patients with lung cancer (LC) were incubated with PBS and 0.2 mg/ml rMBP‑NAP. Antitumor cytokines production was assayed using ELISA and reverse transcription‑quantitative polymerase chain reaction analysis. The cytolytic activity of PBMCs and the number of Interferon‑γ (IFN‑γ)‑secreting cells were assayed using lactate dehydrogenase and Enzyme‑linked ImmunoSpot assays, respectively. The results from the present study revealed that the expression of IFN‑γ, interleukin (IL)‑2, tumor necrosis factor‑α and IL‑12 of PBMCs from patients with LC and healthy donors were significantly increased following treatment with rMBP‑NAP (P<0.05). Additionally, rMBP‑NAP significantly upregulated the number of IFN‑γ‑secreting cells in PBMCs and prominently increased the cytotoxic activity of PBMCs (P<0.05). Furthermore, the expression of TLR2 was significantly enhanced following rMBP‑NAP stimulation (P<0.05), which indicated that rMBP‑NAP may serve an antitumor role via TLR2 signaling pathways. Overall, these results demonstrated that rMBP‑NAP possesses the potential to be a novel immunomodulatory candidate drug and requires further evaluation in clinical trials.

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