Hyaluronic acid-CD44 signaling defines therapeutic resistance and immunosuppressive microenvironment in peritoneal metastasis of gastric cancer - PubMed
4 days ago
- #Gastric Cancer
- #Immunosuppression
- #Hyaluronic Acid
- Hyaluronic acid (HA)-CD44 signaling plays a key role in therapeutic resistance and immunosuppression in gastric cancer peritoneal metastasis (PM).
- Therapy-resistant PM lesions show collagen accumulation, while therapy-sensitive lesions are characterized by elastic fiber enrichment.
- HA deposition activates CD44 signaling in CD4+ T cells, promoting regulatory T cell (Treg) differentiation via the CD44-IQGAP1-RAC1-SMAD3 pathway.
- Pharmacological inhibition of CD44 reduces Treg expansion and enhances anti-PD-1 therapy efficacy in murine models.
- Targeting HA-CD44 signaling may improve immunotherapy outcomes in gastric cancer PM by overcoming immunosuppression.