About the Cover
Many tumors are infiltrated by tumor-specific T cells. However, because the T cells often express the inhibitory marker PD-1, and the ligand for PD-1 is readily expressed within tumor sites, it has been assumed that the infiltrating T cells are inert or exhausted, basically unable to mount an effective immune response against the tumor. However, evidence suggests that tumor-specific T cells in tumors are activated, so why are they unable to overcome tumors? The Gajewski laboratory has found that a major factor hindering a T cell–mediated immune response is that these activated T cells readily apoptose, that is, die by programmed cell death. By preventing apoptosis, or combining strong costimulation with blockade of inhibitory checkpoints, T cells that expressed PD-1 were able to control tumors. Read more in Horton et al., starting on page 14 of this issue of Cancer Immunology Research. Immunohistochemistry image from the Gajewski lab shows Caspase-3 in aqua and CD8⁺ T cells in pink, within a melanoma metastasis. Artwork by Lewis Long.