A nanounit strategy reverses immune suppression of exosomal PD-L1 and is associated with enhanced ferroptosis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34593794.
- Also identified by DOI 10.1038/s41467-021-25990-w and PMC identifier 8484261.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
In addition to increasing the expression of programmed death-ligand 1 (PD-L1), tumor cells can also secrete exosomal PD-L1 to suppress T cell activity. Emerging evidence has revealed that exosomal PD-L1 resists immune checkpoint blockade, and may contribute to resistance to therapy. In this scenario, suppressing the secretion of tumor-derived exosomes may aid therapy. Here, we develop an assembly of exosome inhibitor (GW4869) and ferroptosis inducer (Fe<sup>3+</sup>) via amphiphilic hyaluronic acid. Cooperation between the two active components in the constructed nanounit induces an anti-tumor immunoresponse to B16F10 melanoma cells and stimulates cytotoxic T lymphocytes and immunological memory. The nanounit enhances the response to PD-L1 checkpoint blockade and may represent a therapeutic strategy for enhancing the response to this therapy.
Medical subject headings
- Antineoplastic Combined Chemotherapy Protocols
- Drug Carriers
- Exosomes
- Ferroptosis
- Melanoma, Experimental
- Skin Neoplasms