Novel role of a tyrosine kinase inhibitor by reversion of immune suppression in renal cell carcinoma.

Abstract

e15122 Background: Immune suppression occurs at a high frequency in renal cell carcinoma (RCC) and might contribute to tumor progression and its reversal might be important for the success of T cell-based immunotherapies. It has recently be shown that sunitinib, a receptor tyrosine kinase inhibitor, could reverse the myeloid-derived suppressor cell (MDSC)-mediated immune suppression and prevent tumor-specific T cell anergy as well as the development of regulatory T cells (Treg). Methods: Monolayer and sphaeroid cultures of RCC cells were treated with various concentrations and for different length of time with sunitinib and the expression of HLA class I pathway components and of members of the B7-H family was determined by RT-PCR and flow cytometry. Results: We here show that sunitinib treatment not only reduce the frequency of MDSC and Treg, but also resulted in an enhanced expression of various components of the HLA class I antigen processing machinery (APM), such as e.g. the peptide transporter TAP, tapasin and the HLA class I molecules, and costimulatory molecules in RCC cells, whereas coinhibitory molecules were downregulated under these treatment modalities. This effect was even more pronounced in sphaeroid RCC cultures, which were even more sensitive to the growth inhibitory activity of sunitinib than monolayer cultures. Conclusions: These data suggest that sunitinib is a potential drug to reverse immune suppression not only at the level of immune cells, but also at the level of tumor cells thereby inducing their immunogenicity. No significant financial relationships to disclose.