Modulating AP-1 enables CAR T cells to establish an intratumoral stemlike reservoir and overcomes resistance to PD-1 blockade - PubMed
5 days ago
- #c-Jun modulation
- #PD-1 blockade
- #CAR T cells
- CAR T cell therapy has limited synergy with immune checkpoint inhibitors.
- Stemlike T cells coexpressing PD-1 and TCF1 mediate responses to PD-1-PD-L1 blockade.
- CAR T cells down-regulated TCF1 and became exhausted in murine lung cancer models.
- Overexpression of c-Jun increased intratumoral PD-1+TCF1+ CAR T cells but did not prevent exhaustion.
- PD-L1 blockade restored c-Jun levels, increased CAR T cells, and enabled near-complete tumor clearance.
- Modulating AP-1 enables CAR T cells to overcome resistance to PD-1-PD-L1 blockade.