Abstract: The present disclosure provides compositions and methods for inhibiting T cell senescence and improving T cell immunotherapies. In particular, inhibitors of group IV A phospholipase A2 are disclosed as useful in modulating the lipid metabolism of cells, in particular effector T cells, such that T reg- and tumor cell-induced cell senescence is abrogated. These methods may be employed with particular utility in adoptive T cell therapies and/or enhanced T cell effector functions in vivo, including those performed in combination with checkpoint blockade therapies.

Abstract: The present disclosure relates to the SALL1 tumor suppressor. Methods of employing SALL1 to treat cancer, as well as the underlying mechanism by which this occurs, also are described.

Abstract: The present disclosure relates to the SALL1 tumor suppressor. Methods of employing SALL1 to treat cancer, as well as the underlying mechanism by which this occurs, also are described.

Abstract: CD8+ regulatory T (Treg) cells and ?? Treg cells profoundly suppress host immune responses and thus protect against autoimmune disease while restricting desired immune responses such as antitumor immunity. Synthetic phosphorothioate-protected, guanosine-containing oligonucleotides can directly reverse the suppressive activity of Treg cells without involving dendritic cells. This effect appears to be transduced by signaling through Toll-like receptor (TLR) 8 and engagement of the MyD88 and IRAK4 molecules in Treg cells, in specific embodiments. Stimulation of Treg cells with natural ligands for human TLR8 recapitulated the effect of the synthetic guanosine-containing oligonucleotides.