Expert lecture explains why exhausted T-cell hierarchy drives waning PD-1 blockade responses

An expert lecture on ImmuneZoom describes exhausted T cells as a proliferative hierarchy of TCF1+ Tpex progenitors, intermediate cells and terminally exhausted cells, maintained by persistent antigen and Tox-driven programming. In a chronic LCMV mouse model, stopping PD-1 blockade for two months after two weeks of treatment re-induced T-cell expansion and improved viral control. Long-term blockade enriched CD22-expressing Tpex cells, and combined PD-1/CD22 blockade or a bispecific antibody restored efficacy and increased intratumoral T cells in the AT3 tumor model.