Jan 15, 2019, Volume 50, Issue 1
In this issue, Kurtulus et al. (181–194) reveal that immune checkpoint blockade (ICB) not only acts on checkpoint receptor-expressing CD8+T tumor-infiltrating lymphocytes (TILs), but also significantly affects the transcriptional and functional profile of TILs lacking expression of PD-1 and other checkpoint receptors. Within the heterogeneous populations of PD-1−TILs, two subsets of cells with memory and effector features expand in response to therapy and contribute to the antitumor response. CD8+TILs are depicted as soldiers recruited to the siege of the castle (tumor). The infantry (PD-1+TILs) attacks the gate armed with a battering ram (ICB antibody therapy). Upon tearing down the castle door, a second line of soldiers (PD-1−TILs) takes over the battle and reinforces the exhausted infantry.