Dual PKC-θ and PKC-α inhibition improves experimental allogeneic BMT. After activation through the CD3-TCR (T-cell receptor) complex, CD28 pathway, or cytokines, PKC-θ and PKC-α play both unique and overlapping roles that culminate in the induction of multiple transcription factors necessary for T-cell activation. Donor T cells deficient in both PKC-θ and PKC-α or post-BMT therapy with a drug that inhibits both PKC-θ and PKC-α led to a profound reduction in inflammatory cytokine secretion with relative preservation of cytolytic function and a GVL effect coincident with markedly reduced GVHD. Professional illustration by Alice Y. Chen.