CLL-immunosuppressive signaling targets Rho-GTPase activation signaling that is reversible with lenalidomide or Ab blockade. Healthy donor allogeneic T cells after primary coculture (48 hours) with treated primary CLL cells (or third-party healthy donor allogeneic B cells) were starved for 5 hours and then incubated with anti–(α)-CD3/CD28 beads. After 45 minutes, cells were lysed and T-cell RhoA (A), Rac1 (B), and Cdc42 (C) activity was measured using G-LISA assays (absorbance at 490 nm). Colored columns show the combined mean activation signal ± SD from 6 CLL patient functional screens. Healthy donor T cells treated alone with CD3/CD28 or control IgG beads were included as controls. *P < .05.