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Nicotine Stimulated Dendritic Cells Could Achieve Anti-Tumor Effects in Mouse Lung and Liver Cancer

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Abstract

Introduction

Our previous studies have revealed that nicotine-treated immature dendritic cells (imDCs) have anti-tumor effects in murine lymphoma models. The present study is to explore the preventive and therapeutic anti-tumor effects of nicotine-treated imDCs in murine lung and liver cancer.

Materials and Methods

To address this objection, bone marrow-derived imDCs were firstly stimulated by nicotine in vitro and the expressions of CD80, CD86, CD40, CD11b, MHC class I and II were determined by flow cytometry. Then, DCs-dependent tumor-lysate-specific T cell proliferation, IL-12(p40+p70) secretion were determined by BrdU cell proliferation assay and enzyme-linked immunosorbent assay, respectively. The anti-tumor effects of such imDCs were further explored by intraperitoneal transfer against tumor challenge or implantation. By using kinase inhibitors, the mechanism of nicotine upregulating CD80 was finally explored by flow cytometry.

Results

The results showed that: firstly, nicotine could upregulate the expressions of CD80, CD86, CD40,CD11b, MHC class I and II molecules in imDCs. Secondly, nicotine could promote imDCs-dependent T cell priming and IL-12 secretion. Most importantly, systemic transfer of ex vivo nicotine-stimulated imDCs, which enhanced CD80 expression through PI3K activation, could reveal preventive and effectively therapeutic effects on tumor development.

Conclusions

Ex vivo nicotine stimulation can significantly improve imDCs efficacy for adaptive therapy of cancer. Nicotine-treated imDCs might be considered as a potential candidate for therapeutic tumor immunotherapy for lung and liver cancer.

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Abbreviations

imDCs:

immature dendritic cells

DCs:

dendritic cells

nAChR:

nicotinic acetylcholine receptor

LLC:

Lewis lung cancer

MAPK:

mitogen-activated protein kinase

PI3K:

phosphatidylinositol-3-kinase

Ni:

nicotine

BTX:

α-bungarotoxin

TC:

tubocurarine chloride

FACS:

flow cytometry

MLRs:

mixed lymphocyte reactions

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Acknowledgments

The project was supported by the Natural Science Foundation of Fujian Province of China (No.2008J0112) and the grant from the National Laboratory for Oncogenes and Related Genes of China (90-08-02). We thank Professor Cao XT (Second Military Medical University, Shanghai, China) and Chen YH (University of Pennsylvania, Philadelphia, USA) for kindly providing Hepa 1-6 cell lines and polishing manuscripts. Also, we thank Mingxia Yan, Jinhua Su, and Ming Yao for excellent animal care. JR Gu designed the research and polished the paper. FG Gao and HT Li performed research and analyzed data. ZJ Li contributed to laboratory support.

Disclosure Statement

The authors declare no competing financial interests.

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Authors and Affiliations

  1. Department of Basic Medicine Science, Medical College, Xiamen University, Xiamen, 361005, People’s Republic of China

    Feng Guang Gao, Hai Tao Li & Zhi Jing Li

  2. State Key Laboratory for Oncogenes and Related Genes, Cancer Institute of Shanghai Jiao Tong University, Shanghai, 200030, People’s Republic of China

    Feng Guang Gao & Jian Ren Gu

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  1. Feng Guang Gao
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  2. Hai Tao Li
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  3. Zhi Jing Li
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Correspondence to Jian Ren Gu.

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Gao, F.G., Li, H.T., Li, Z.J. et al. Nicotine Stimulated Dendritic Cells Could Achieve Anti-Tumor Effects in Mouse Lung and Liver Cancer. J Clin Immunol 31, 80–88 (2011). https://doi.org/10.1007/s10875-010-9459-5

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  • DOI: https://doi.org/10.1007/s10875-010-9459-5

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