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Immunology

Sorafenib inhibits activation of human peripheral blood T cells by targeting LCK phosphorylation

Leukemia volume 22, pages 1226–1233 (2008)Cite this article

Abstract

Sorafenib, a novel drug for metastatic renal cancer, has broad-spectrum activity against multiple tyrosine kinases, including Raf-1, vascular endothelial growth factor receptor and platelet-derived growth factor receptor. However, little is known about its effects on the immune system. In this report, we examine the effects of sorafenib on the proliferation and activation of human peripheral blood T cells, as well as its effects on T-cell-mediated immune response in mice. At concentrations similar to those used in patients, sorafenib inhibited the proliferation of primary human T cells in vitro. At more than 10 μM, sorafenib caused an irrecoverable inhibition of proliferation, even after drug withdrawal. In addition, sorafenib induced T-cell apoptosis at concentrations higher than 10 μM. sorafenib also caused G0/G1 phase arrest, inhibition of CD25 and CD69 expression, interleukin-2 production and LCK phosphorylation in the T cells; all of these effects exhibited dose and time dependence. When tested against contact dermatitis in mice, sorafenib significantly reduced the ear swelling induced by picryl chloride. These findings suggest that sorafenib may cause the loss of T-cell immune response by inducing apoptosis and targeting LCK. This could potentially lead to immunosuppression in patients with cancer.

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Acknowledgements

This work was supported by National Science Foundation of China no. 30730107, the 973 Program of China no. 2002CB513000 and the Provincial Science Foundation of Jiangsu no. BK2007246. This study was carried out in Nanjing University.

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  1. W Zhao and Y H Gu: These authors contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China

    W Zhao, Y H Gu, R Song, B Q Qu & Q Xu

  2. Department of Clinical Oncology, Jiangsu Province Hospital, Nanjing, China

    Y H Gu

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  1. W Zhao
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Correspondence to Q Xu.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Zhao, W., Gu, Y., Song, R. et al. Sorafenib inhibits activation of human peripheral blood T cells by targeting LCK phosphorylation. Leukemia 22, 1226–1233 (2008). https://doi.org/10.1038/leu.2008.58

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