biostudies-literatureUnknown12(1)Wang GIn 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 therapeutiNature communications5733https://www.ebi.ac.uk/biostudies/studies/S-EPMC8484261biostudies-literatureA nanounit strategy reverses immune suppression of exosomal PD-L1 and is associated with enhanced ferroptosis.PMC8484261Li WSang WYan JLi JZhang ZTian HTian YXie LWang GLi BDai YfalseA 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 therapeuti2021-01-01T00:00:00Z2021 Sep2025-04-21T17:34:58.053Z2025-04-21T17:34:58.053ZS-EPMC84842613459379410.1038/s41467-021-25990-w