Targeting IFN-γ signaling and S100a9 on GVHD/GVT. (A) IFN-γ signaling on donor T cells reduces S100a9 production and is associated with T-cell trafficking to the gut and GVHD target tissues. Alteration of this pathway by antibody-mediated blockade of IFN-γ receptor binding (B), deletion of IFN-γ receptor on donor T cells, or transduction of S100a9, resulting in overexpression, all of which result in increased production of S100a9 (C), or administration of S100a9 results in reduced T-cell trafficking to GVHD target tissues, such as the gut, and suppresses GVHD while still allowing for GVL (D). IFNγR, interferon-gamma receptor. Professional illustration by Somersault18:24.