Retinoblastoma cell-derived Twist protein promotes regulatory T cell development

Background The development of tumor tissue-infiltrating regulatory T cell (Treg) is incompletely understood. This study investigates the role of retinoblastoma cell (Rbc)-derived Twist‑related protein 1 (Twist) in the Treg development. Methods The surgically removed Rb tissues were collected. Rbcs were cultured with CD4 + T cells to assess the role of Rbc-derived Twist in the Treg generation. Results We found that more than 90% Rbcs expressed Twist. Foxp3 + Tregs were detected in the Rb tissues that were positively correlated with the Twist expression in Rbcs, negatively associated with Rb patient survival and sight survival. Treating Rbcs with hypoxia promoted the Twist expression that could be detected in the cytoplasm, nuclei and on the cell surface. Twist activated CD4 + T cells by binding the TLR4/myeloid differentiation factor 2 complex and promoted the transforming growth factor-β-inducible early gene 1 product and Foxp3 expression. These Rbc-induced Foxp3 + Tregs showed immune-suppressive function on CD8 + T cell proliferation. Conclusions Rbcs express Twist, that induces IL-4 + Foxp3 + Tregs; the latter can inhibit CD8 + cytotoxic T cell activities. Therefore, Twist may play an important role in the pathogenesis of Rb.