Abstract
BACKGROUND/AIM: The clinical response rate of prostate cancer to tyrosine kinase inhibitor (TKI) monotherapy is low. The mechanisms of resistance to TKI are unclear. This study aimed to examine if the tumor microenvironment (TME) is involved in the resistance. MATERIALS AND METHODS: The anti-vascular effect of Sutent was examined by immunofluorescent staining in TRAMP-C1 tumor. The percentage of CD11b(+) population were analyzed by flow cytometry. The level of cytokines and chemokines were measured by multiplex immunoassay. RESULTS: The Sutent monotherapy caused 1.5 days of tumor growth delay, chronic hypoxia, and more mature vasculature. Sutent monotherapy increased the percentage of polymorphonuclear myeloid-derived suppressor cells (MDSCs) in peripheral blood. The evolved TME triggered the re-distribution of myeloid cells in chronically hypoxic areas. The multiplex immunoassay indicated higher levels of several cytokines and chemokines both in tumors and the blood. CONCLUSION: Sunitinib treatment induced a distinct tumor microenvironment that impaired the efficient reduction of MDSCs by TKI.