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The CIK cells stimulated with combination of IL-2 and IL-15 provide an improved cytotoxic capacity against human lung adenocarcinoma

  • Research Article
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Tumor Biology

Abstract

Generation of cytokine-induced killer (CIK) cells is an emerging approach in adoptive donor lymphocyte infusion for patients with a wide range of tumors. However, our previous in vitro studies have shown that the killing efficacy of CIK cells against lung cancer was lower than other tumor cells, while the underlying mechanisms are not clear. We explored the feasibility to improve CIK cells mediated cytotoxicity against lung cancer. Interleukin (IL)-15 is a pleiotropic cytokine that stimulates cytolytic activity and cytokine secretion of NK cells, which may enhance the cytotoxic activity of CIK cells. In this study, we intended to stimulate the CIK cells by IL-2 in combination with IL-15 in cell expansion to achieve enhanced cytotoxicity against lung cancer cells. The different phenotypes of IL-2 or combination of IL-2 and IL-15 stimulated cytokine-induced killer cells were determined, and the improved cytotoxicity of IL-2 and IL-15 induced CIK cells against lung adenocarcinoma were evaluated both in vitro and in vivo. CIK cells stimulated with both IL-2 and IL-15 has shown greater proliferative potential than CIK cells treated with IL-2 alone. IL-15 induction also has driven the expansion of CD3+CD56+ subset and significantly enhanced cytotoxicity against tumor cells. Further analysis has demonstrated that CIKIL-2&IL-15 injected mice models have shown significant tumor regression and lower expression level of CyclinD1 in tumor tissue. This study has provided preclinical evidences that CIKIL-2&IL-15 with enhanced cytotoxicity may offer alternative treatment option for patients with lung cancer.

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Acknowledgments

This work is supported by grants from National Natural Science Foundation of China (no. 81160267) and grants from the “Special and Joint Program” of Yunnan Province Science and Technology Department and Kunming Medical University (no. 2010CD211). We give sincere thanks to Professor Dagang Liu for his efforts in immunohistochemistry assays and Mr. Weiwei Tang for his effort in flow cytometry assays.

Conflicts of interest

There is no potential conflict of interest in this study.

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Authors and Affiliations

  1. Yan’an Affiliated Hospital of Kunming Medical University, No. 245 East of Renmin Road, Kunming, 650051, Yunan, People’s Republic of China

    Chuanyu Wei, Wenju Wang, Wei Pang, Mingyao Meng, Lihong Jiang, Sha Xue, Yanhua Xie, Ruhong Li & Zongliu Hou

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  1. Chuanyu Wei
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  2. Wenju Wang
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  3. Wei Pang
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  6. Sha Xue
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  7. Yanhua Xie
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  8. Ruhong Li
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  9. Zongliu Hou
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Correspondence to Zongliu Hou.

Additional information

C. Wei and W. Wang contributed equally to this work.

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Wei, C., Wang, W., Pang, W. et al. The CIK cells stimulated with combination of IL-2 and IL-15 provide an improved cytotoxic capacity against human lung adenocarcinoma. Tumor Biol. 35, 1997–2007 (2014). https://doi.org/10.1007/s13277-013-1265-2

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  • DOI: https://doi.org/10.1007/s13277-013-1265-2

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