Tumor specific TGF-β insensitive CD8 + T cells augments the antitumor effect through inhibition of epithelial-mesenchymal transition in CD 105 + renal carcinoma stem cells

Abstract

Background The CD105+ cell clones isolated from renal cell carcinoma (RCC)were characterized as cancer stem cells. This study aimed to explore the antitumor mechanism of the transform growth factor-β(TGF-β) insensitive CD8+ T cells against CD105+ cells in vitro and vivo. Methods The CD105+ cell clones were isolated from primary RCC cell lines and characterized by the immunofluorescence, qRT-PCR and western-blotting analysis. The expression levels of TGF-β1 were examined in 105 RCC tissues and correlation regression analysis were performed. The tumor specific TGF-beta insensitive CD8+ T cells were expanded ex vivo as previously described. The naïve CD8+ T cells and PBS as control. The humanized SCID mice were challenged with injection of CD105+ cells before adoptive transfer. The antitumor appraisal including survival analysis, tumor burden and bioluminescent imaging examination. The presence of pulmonary metastases was evaluated pathologically and epithelial-mesenchymal transition related molecular were analyzed. Results The CD105+ cells were characterized with renal cancer stem cell for the high expression of Nanog, Oct4, Vimentin, Pax2 and high tumorigenicity. The TGF-beta-insensitive CD8+T cells showed the specific antitumor effect against CD105+ in vitro, were associated with suppressed pulmonary metastasis, and prolonged survival times, inhibited the epithelial-mesenchymal transition in tumor microenvironment. Conclusion Our results demonstrate that the TGF-beta insensitive CD8+T cells show the tumor-specific antitumor effect including reduce tumor burden, inhibit pulmonary metastasis by blockade the EMT mechanism existed in CD105+CSCs. This study may provide a new perspective and method for the immunotherapy in RCC.