Work

PD-L1 transmembrane domain substitution overcomes CAR-T exhaustion driven by tonic signaling

Year: 2026

Type: article

Abstract: . Mechanistically, these benefits were associated with attenuated phosphorylation across the CD3ζ-ZAP70-PLC-γ1/MAPK/AKT/NF-κB axis, downregulation of exhaustion-associated genes, and upregulation of stemness- and memory-related programs. Collectively, our findings establish that the PD-L1 TM swap is a modular and broadly applicable strategy to suppress CAR tonic signaling and promote durable, memory-biased CAR-T responses against solid tumors.

Source: Molecular Therapy Oncology

DOI: 10.1016/j.omton.2026.201364