Mobilized stem cell grafts from patients with myeloma contain a high number of both immunosuppressive Tregs and effector CD8 T cells. These Tregs limit the tumoricidal effect during autologous stem cell transplantation. However, depletion of Tregs or activation of CD8 with an interleukin 2 (IL-2)/IL-15 agonist (NL-201) leads to expanded polyfunctional CD8 T cells, which ultimately improves antimyeloma immunity after autologous stem cell transplantation. IFN, interferon.