Expert lecture: exhausted T-cell hierarchy explains waning PD-1 blockade responses
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An expert lecture on ImmuneZoom frames T-cell exhaustion as a proliferative hierarchy: TCF1+ Tpex progenitor cells, intermediate cells, and terminally exhausted cells, sustained by persistent antigen and Tox-driven programming. In a chronic LCMV mouse model, interrupting PD-1 blockade — stopping treatment after two weeks and resuming after two months — re-induced T-cell expansion and improved viral control. The lecture also reports that long-term PD-1 blockade enriched Tpex cells expressing CD22, and that combined PD-1/CD22 blockade or a bispecific antibody restored efficacy and increased intratumoral T cells in the AT3 tumor model. The work suggests treatment scheduling and combination strategies could counteract the loss of responsiveness seen with prolonged PD-1 blockade.
Written by a model from the reports · updated 2 hours ago
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- youtube.comExpert 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.
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