Immune checkpoint blockade is efficacious in some cancers, but resistance to therapy can occur, and the mechanisms behind this are still not fully understood. Fu et al. find that T-cell exhaustion contributes to therapy resistance. By evaluating T cell–intrinsic diacylglycerol kinase alpha (Dgka), it is revealed that Dgka plays a major role in regulating T-cell exhaustion in the tumor microenvironment of solid tumors by modulating T-cell intracellular signaling. Dgka also mediates tumor cell signaling and growth, highlighting a dual tumor–immune role. Inhibition of Dgka prolongs T-cell antitumor responses and, thus, increases efficacy of anti–PD-1 therapy against solid tumors. The study reveals that inhibition of Dgka has dual effects on T-cell invigoration and tumor cell growth and that when it is combined with immune checkpoint blockade, antitumor responses are enhanced. Read more in this issue on page 371. Original image from Fig. 7A. Artwork by Lewis Long.