A nanounit strategy reverses immune suppression of exosomal PD-L1 and is associated with enhanced ferroptosis

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 (Fe3+) 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. PD-L1 is frequently expressed on the surface of cancer cells and can be excreted from cancer cells in exosomes. Here, the authors generate a nanotherapy that combines an inhibitor of exosome production and an inducer of ferroptosis, enhancing the response to immune checkpoint blockade therapy.

Automated summary

This study reveals the ability of exosomal PD-L1 to inhibit T cell activity and confer resistance to immune checkpoint blockade therapy. By combining an exosome inhibitor and a ferroptosis inducer in a nanotherapy, the response to anti-tumor immune responses is enhanced, particularly in the context of PD-L1 checkpoint blockade.