Modulation of immune cell subpopulations in renal cell carcinoma patients by sunitinib.

Abstract

395 Background: Increased numbers of immune suppressive cells, such as regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSC) as well as alterations in the frequency and function of activated and memory T cells in peripheral blood mononuclear cells (PBMNC) represent immune escape mechanisms of renal cell carcinoma (RCC). The tyrosine kinase inhibitor sunitinib, which is currently successfully implemented in the treatment of RCC has been shown to modulate immune suppressive cells as well as T lymphocytes thereby shifting the immune balance in these patients to a more stimulating setting. Methods: Using flow cytometry and a large panel of antibodies directed against different immunomodulatory molecules, we here analysed the effects of (i) adjuvant sunitinib treatment (50 mg for 4 weeks, on 2 weeks off) on the composition of various immune cell populations, their function and activity in RCC patients and (ii) sunitinib treatment of PBMNC from healthy donors over time Results: A time-dependent decrease in the frequency of Treg and MDSC was found in PBMNCs during in vitro and in vivo sunitinib treatment. In addition, the number of NK cells, activated and/or memory T cells was increased in PBMNC of TKI-treated patients over time. Conclusions: This observation may have important implications for (i) the monitoring of the sunitinib activity on immune cells, (ii) the treatment schedule including duration of TKI therapy, and (iii) the implementation of sunitinib in combination with immunotherapies in RCC patients. Long-term monitoring of a larger patients' group will show whether the activation of T cells and NK cells as well as the decrease of immune suppressive cells due to sunitinib treatment is associated with enhanced antitumor responses. [Table: see text]