KIF4A promotes tumor progression of bladder cancer via CXCL5 dependent myeloid-derived suppressor cells recruitment

Abstract

AbstractAlthough KIF4A has been found to play an important role in a variety of tumors and is closely associated with the activation of immunocytes, its role in bladder cancer (BC) remains unclear. Here, we report increased expression of KIF4A in both lymph node-positive and high grade BC tissues. High expression of KIF4A has been significantly correlated with fewer CD8+ tumor-infiltrating lymphocytes (TILs) and a much worse prognosis in patients with BC. With respect to promoting tumor growth, the expression of KIF4A in promoting tumor growth was more pronounced in immune-competent mice (C57BL/6) than in immunodeficient mice (BALB/C). In addition, the more increased accumulation of myeloid-derived suppressor cells (MDSCs) was observed in tumor-bearing mice with KIF4A overexpression than in the control group. Transwell chemotaxis assays revealed that KIF4A overexpression in T24 cells increased MDSC recruitment. Furthermore, according to ELISA results, CXCL5 was the most noticeably increased cytokine in the KIF4A-transduced BC cells. Additional studies in vitro and in vivo showed that the capability of KIF4A to promote BC cells to recruit MDSCs could be significantly inhibited by anti-CXCL5 antibody. Therefore, our results demonstrated that KIF4A-mediated BC production of CXCL5 led to an increase in MDSC recruitment, which contributed to tumor progression.