Immunologic effects of sunitinib in renal cell carcinoma

2008 
14551 Background: Sunitinib is a multi-targeted tyrosine kinase inhibitor with proven efficacy against renal cell carcinoma (RCC). Sunitinib demonstrates immunomodulatory characteristics which may potentially augment the potency of tumor vaccines. We examined the effect of sunitinib therapy on measures of cellular immunity and its ability to reverse tumor associated immune suppression mediated by regulatory T cells (Tregs) and the inhibitory molecule PD-L1 (programmed cell death ligand-1). Methods: Peripheral blood was collected in RCC patients pre- and post-sunitinib therapy. Phenotypic and functional characteristics of circulating T cells and dendritic cells (DC) were determined. Levels of Tregs (CD4+/CD25+/FOXP3+) were quantified. In vitro effects of sunitinib on the expression PD-L1 by RCC were assessed by flow cytometry and western blot analysis. Results: A significant increase in T cell activity was observed after one month of sunitinib therapy as manifested by enhanced proliferative responses to ph...
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