Dauricine lowers T-cell PD-1 through lysosomal degradation and curbs melanoma growth
- The natural alkaloid dauricine reduced PD-1 levels in Jurkat T cells via the endosomal–lysosomal route, accompanied by increased ubiquitination.
- Lower PD-1 coincided with stronger T-cell killing of melanoma cells; dauricine also directly caused apoptosis and G1 arrest in the tumor cells.
- In melanoma xenograft mice it increased T-cell infiltration and slowed tumor growth.
💡 Points Based on the abstract
Dauricine hits tumor cells directly, so the xenograft benefit can't be credited to PD-1 loss. Worse, a standard xenograft needs immunodeficient hosts, which undercuts a T-cell mechanism; a syngeneic model with PD-1 reconstitution or a degradation-resistant PD-1 mutant would settle it. Target-binding evidence is also absent: what engages PD-1 or its trafficking machinery is still unknown.