The antitumor effects of histone deacetylase inhibitors (HDACi) are repressed in immunocompromised mice. Rag-2γ^−/−mice transplanted with Eμ-myc B-cell lymphomas and treated with HDACi succumb significantly earlier than wild-type tumor-bearing mice and die with high splenic tumor burden as shown in this image (magnification, ×10). HDACi are able to inhibit their target enzymes and mediate tumor cell apoptosis in immunocompromised mice, however, in the absence of a functional immune system, the therapeutic efficacy of HDACi is significantly diminished. These data demonstrate the importance of a host immune system for sustained antitumor responses mediated by HDACi and indicate that these agents could be combined with immunotherapy to enhance efficacy. For details, see article by West and colleagues on page 7265.