Abstract
Abstract Immune suppression is frequently detected in renal cell carcinoma (RCC) and might contribute to tumor progression. Recently, receptor tyrosine kinase inhibitors have been shown to revert the frequency of the myeloid-derived suppressor cell (MDSC)-mediated immune suppression, the development of regulatory T cells (Treg), increase the number of NK cells and prevent tumor-specific T cell anergy. The mTOR inhibitors exhibit a unique target profile resulting in both anti-tumor and anti-angiogenic activity. It has been shown that everolimus can induce apoptosis in various cancers of distinct origin. However, the role of everolimus on immune cell subpopulations have not yet been studied in detail. Therefore peripheral blood mononuclear cells as well as human CD3+ T cells obtained from healthy blood donors were either left untreated or stimulated with antibodies or PHA and subjected to multicolour flow cytometry using a large set of antibodies. We here show that everolimus exerts different effects on peripheral blood mononuclear cells regarding the composition of immune cell subpopulations, their proliferation, activation, cytokine production and degranulation. Upon everolimus treatment the number of stimulated CD3+, CD4+ and CD8+ and CD4+/FoxP3* T cells decreased, whereas the number of NK cells, CD4+/CD8+ CD45RO T cells increased. Furthermore, the T cell proliferation was reduced upon mTOR inhibitor treatment. These data suggest that everolimus modulates the composition of immune cells, their activation and growth properties, which is important for the design of combinatorial therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 641. doi:10.1158/1538-7445.AM2011-641
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