Combating small extracellular vesicle-mediated immunological barriers in the tumor microenvironment via strategically activatable PEGylated peptides - PubMed
2 hours ago
- #tumor microenvironment
- #exosomes
- #cancer immunotherapy
- Introduces ExoPERM, a pH-responsive system using PEGylated peptides to disrupt tumor-derived small extracellular vesicles (TDEs) in the tumor microenvironment (TME).
- The system targets mildly acidic TME conditions (pH 6.5) to selectively release peptides, breaking down TDEs and blocking PD-L1 interactions with PD-1 on CD8+ T cells.
- Disruption of TDEs reduces immunosuppression and cancer-associated fibroblast activation, helping remodel fibrotic stroma for improved immune cell infiltration.
- In vivo studies show enhanced CD8+ T-cell activity when combined with immune checkpoint blockade or adoptive T-cell transfer, converting cold tumors into hot tumors.
- Validated in mouse melanoma and colorectal cancer models, offering a novel strategy to overcome TDE-mediated resistance in cancer immunotherapy.