Fig. 24

(Abstract P2). (i, ii) Under pathological conditions such as cancer, TGF-β production by tumor cells binds to cognate receptors on T cell surfaces and triggers signaling events that lead to Foxp3 expression and induced Treg cell development. (iii-iv) Signaling via the TGF-β non-canonical Akt-hnRNP E1-axis leads to post-transcriptional moesin expression. The TGF-β signaling pathway, Rho kinase and/or Phosphatidylinositol 4,5-bisphosphate[PtdIns(4,5)P2] pathways, lead to phosphorylation/activation of moesin and aids moesin binding to the F-actin. (v-viii) Moesin-F-acting binding may promote internalization of TGF-β receptors possibly via early endosomes which feeds forward to promote optimal TGF-β signaling leading to efficient Foxp3 induction and iTreg cell differentiation. (ix) Moesin may also promote efficient recycling of TGF-β receptors to maintain the abundance of TβRII on the cell surface. (x) Differentiated induced Treg cells then suppress the proliferation of other immune cells such as cytotoxic T lymphocytes and effector T (Teff) cells to limit anti-tumor responses and promote tumor progression