Dual PD-1/IL-2Rα targeting restores CD8+ T cell fitness via STAT5/CD47 axis in SMARCA4-deficient NSCLC - PubMed
9 hours ago
- #SMARCA4-deficient NSCLC
- #CD8+ T cell fitness
- #PD-1/IL-2 bispecific antibody
- SMARCA4-deficient NSCLC is a clinically aggressive subtype resistant to immune checkpoint inhibitors.
- SMARCA4 deficiency disrupts IL-2-STAT5 signaling in CD8+ T cells by suppressing IL-2Rα (CD25) expression, leading to T cell exhaustion.
- A PD-1/IL-2 bispecific antibody (bsAb) restores STAT5 activation and effector function in exhausted CD8+ T cells by co-engaging PD-1 and delivering IL-2 signals.
- STAT5 activation upregulates CD47 on CD8+ T cells, protecting them from macrophage-mediated phagocytosis and enhancing survival in the tumor microenvironment.
- The IL-2-STAT5-CD47 axis plays a role in immune evasion, and targeting it with PD-1/IL-2 bsAb may overcome resistance in SMARCA4-deficient NSCLC.