PD-1 blockade drug holiday improves exhausted progenitor CD8 T cell (Tpex) reinvigoration by avoiding Tpex adaptive resistance - PubMed
4 hours ago
- #PD-1 blockade
- #T cell exhaustion
- #Drug holiday
- Intermittent PD-1 blockade with a drug holiday allows for secondary reinvigoration of exhausted T cells (Tex) and improves disease control, unlike continuous treatment which only provides a single peak.
- Long-term continuous PD-1 blockade erodes the proliferative and differentiation capacity of progenitor exhausted CD8 T cells (Tpex), while a drug holiday restores this ability by avoiding adaptive resistance.
- Adaptive resistance in Tpex during prolonged PD-1 blockade involves sustained expression of the inhibitory receptor CD22; co-blockade of PD-1 and CD22 enhances Tex reinvigoration and disease control.
- The findings suggest clinical implications for optimizing PD-1 blockade regimens through intermittent dosing and combination therapies to improve immune pharmacodynamics in chronic infections and cancer.