Cancer patients are often treated with allogenic bone marrow transplantation followed by donor lymphocyte infusion (which contains NK cells) in order to induce antitumor responses; however, this therapy is often associated with life-threatening graft-versus-host disease (GvHD). Many strategies have been employed to limit GvHD, such as donor T-cell depletion, but more robust methods are needed. Here, the authors show that without prior bone marrow transplantation, donor lymphocyte infusion controls melanoma tumor growth in mouse models without inducing GvHD; these effects associate with the expansion and activation of tumor-infiltrating NK cells. Blocking IL2 from host CD4⁺ T cells inhibits the NK-cell–mediated antitumor effects of donor lymphocyte infusion. Together, these data demonstrate that host CD4⁺ T cells support the NK-cell–mediated antitumor effects of donor lymphocyte infusion via IL2. To read more, Dang et al. begins on page 756. Hematoxylin and eosin staining from the Sprangers laboratory. Artwork by Lewis Long.