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A nanounit strategy reverses immune suppression of exosomal PD-L1 and is associated with enhanced ferroptosis
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A nanounit strategy reverses immune suppression of exosomal PD-L1 and is associated with enhanced ferroptosis
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Journal Article
A nanounit strategy reverses immune suppression of exosomal PD-L1 and is associated with enhanced ferroptosis
2021
Overview
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
3+
) 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.
