Immune regulation for renal cell carcinoma

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1) Recent reports showed that vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) might be involved to defective function of dendritic cells, leading to poor prognosis due to failure of immunotherapy. To test hypothesis, we measured serum levels of VEGF and IL-6 in RCC patients. Patients with elevated levels of VEGF and IL-6 had worse prognosis, suggesting that these factors (VEGF and IL-6) might affect dendritic cell dysfunction.2) Among various factors which induce and proliferation and differentiation of dendritic cells, we focused on FLT-3 ligand-FLT-3 pathway, because interestingly FLT-3 is expressed in RCC cell lines. FLT-3 ligand did not affect the cell growth in RCC cell lines in vitro. About 20-30% of acute myeloid leukemia patients show genetic mutations of FLT-3, which leads to constitutive activation of FLT-3 activity. We hypothesized a similar mechanism as cause of fFLT-3 expression in RCC. However, no mutation was seen in RCC cell lines, indicating other mechanism than known mutation of FLT-3. The protein kinase inhibitor SU5614 failed to inhibit the cell growth to RCC cell lines in vitro. However, FLT-3 might be still a new target for treating RCC patients.