Transforming growth factor-β 1 deteriorates microrheological characteristics and motility of mature dendritic cells in concentration-dependent fashion

Abstract

Dendritic cells (DCs) are potent and specialized antigen-presenting cells that play a crucial role in initiating and amplifying both the innate and adaptive immune responses. Tumor cells can escape from immune attack by secreting suppressive cytokines which solely or cooperatively impair the immune function and microrheological properties of DCs. However, the underlying mechanisms are not fully defined. Transforming growth factor-β₁ (TGF-β₁) has been identified as a major cytokine in the tumor microenvironment. To determine the effects of TGF-β₁ on mature DCs (mDCs) from microrheological viewpoint, cells were treated with different concentrations of TGF-β₁. The results showed that the impaired microrheological parameters, including osmotic fragility, electrophoretic mobility, deformability, membrane fluidity, F-actin organization and so on, as well as motilities of mDCs relied heavily on TGF-β₁ concentration. Moreover, these changes were correlated with the expression levels of fascin1, cofilin1, phosphorylated cofilin1 and profilin, this could be one of the crucial aspects of immune escape mechanisms of tumors, hinting that the signal pathway of TGF-β₁ should be blocked in appropriate way before performing DCs-based immunotherapy against cancer. It is clinically important to understand the biological behavior of DCs and immune escape mechanism of tumor as well as how to improve efficiency of the anti-tumor therapy based on DCs.