Sunitinib impairs the proliferation and function of human peripheral T cell and prevents T-cell-mediated immune response in mice

Copyright 2009 Elsevier Inc. All rights reserved.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 135(2010), 1 vom: 12. Apr., Seite 55-62
1. Verfasser: Gu, Yanhong (VerfasserIn)
Weitere Verfasser: Zhao, Wei, Meng, Fanyu, Qu, Bingqian, Zhu, Xu, Sun, Yang, Shu, Yongqian, Xu, Qiang
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2010
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Antineoplastic Agents Cytokines Indoles Pyrroles Sunitinib V99T50803M Picryl Chloride Z4ZG7O5SZ9
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520 |a Sunitinib (sunitinib malate; SU11248; SUTENT) is a novel multi-targeted receptor tyrosine kinase inhibitor currently approved for the treatment of metastatic renal cell carcinoma. To analyze the possible use of this compound in combination with immunotherapeutic approaches, we investigated the effects of sunitinib on the human peripheral T cells and the induction of primary immune responses in mice. Sunitinib inhibited the proliferation of primary human T cells from normal healthy volunteers as well as from renal cell carcinoma (RCC) and other cancer patients. The inhibition was recoverable after drug withdrawal because sunitinib did not induce T-cell apoptosis even at 0.8 muM. In addition, sunitinib led to accumulation in G(0)/G(1) phase of the cell cycle, inhibition of cytokine production, downregulation of activation markers expression and blockade of Zap-70 signaling in the T cells. Sunitinib significantly reduced the ear swelling induced by picryl chloride in mice. In light of these findings, the effects of sunitinib on the immune system should be emphasized for the therapy of metastatic renal cell carcinoma patients to avoid the impairment of T lymphocytes 
650 4 |a Journal Article 
650 4 |a Research Support, Non-U.S. Gov't 
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650 7 |a Cytokines  |2 NLM 
650 7 |a Indoles  |2 NLM 
650 7 |a Pyrroles  |2 NLM 
650 7 |a Sunitinib  |2 NLM 
650 7 |a V99T50803M  |2 NLM 
650 7 |a Picryl Chloride  |2 NLM 
650 7 |a Z4ZG7O5SZ9  |2 NLM 
700 1 |a Zhao, Wei  |e verfasserin  |4 aut 
700 1 |a Meng, Fanyu  |e verfasserin  |4 aut 
700 1 |a Qu, Bingqian  |e verfasserin  |4 aut 
700 1 |a Zhu, Xu  |e verfasserin  |4 aut 
700 1 |a Sun, Yang  |e verfasserin  |4 aut 
700 1 |a Shu, Yongqian  |e verfasserin  |4 aut 
700 1 |a Xu, Qiang  |e verfasserin  |4 aut 
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