Journal
CLINICAL IMMUNOLOGY
Volume 135, Issue 1, Pages 55-62Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2009.11.013
Keywords
Sunitinib; T-cell activation; Metastatic renal cell carcinoma; Contact hypersensitivity
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Funding
- National Science Foundation of China [30730107, 90913023]
- Provincial Science Foundation of Jiangsu [BK2007246, BK2007716]
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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 mu M. 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 tight 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. (C) 2009 Elsevier Inc. All rights reserved.
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