Targeting tumor-associated sympathetic nerves orchestrates tertiary lymphoid structures to enhance PD-1/PD-L1 blockade efficacy - PubMed
5 hours ago
- #Sympathetic nerves
- #Immunotherapy
- #Gastric cancer
- High TH+ fiber density in gastric cancer (GC) is linked to poorer survival and reduced response to immune checkpoint blockade (ICB).
- Sympathetic innervation inversely correlates with CXCL13+ CD8+ T-cell infiltration and tertiary lymphoid structure (TLS) abundance.
- Chemical sympathectomy in murine models suppressed tumor growth, enhanced CXCL13+ CD8+ T-cell function, promoted TLS formation, and reduced metastasis.
- Sympathetic neural activity inhibits CD8+ T-cell-mediated anti-tumor immunity via β-adrenergic signaling.
- Combining β-blocker Atenolol with αPD-L1 therapy synergistically enhances anti-tumor immunity.
- Pan-cancer analyses show negative associations between TH expression, immune activation, and αPD-1 therapy benefit.
- Targeting adrenergic signaling may improve immunotherapy outcomes by promoting CXCL13+ CD8+ T cells and TLS formation.