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...

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Bibliographic Details
Published in:Nature communications 2021-09, Vol.12 (1), p.5733-5733, Article 5733
Main Authors: Wang, Guohao, Xie, Lisi, Li, Bei, Sang, Wei, Yan, Jie, Li, Jie, Tian, Hao, Li, Wenxi, Zhang, Zhan, Tian, Ye, Dai, Yunlu
Format: Article
Language:English
Subjects:
13/1
13/21
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631/67/1059/2325
639/301/54/152
639/301/54/990
Apoptosis
Cancer
Cytotoxicity
Exosomes
Ferroptosis
Health sciences
Humanities and Social Sciences
Hyaluronic acid
Immune checkpoint
Immunological memory
Immunology
Immunotherapy
Inhibitors
Iron
Ligands
Lipids
Lymphocytes
Lymphocytes T
Melanoma
Memory cells
multidisciplinary
PD-L1 protein
Science
Science (multidisciplinary)
Strategy
Therapy
Tumor cells
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Summary: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.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-021-25990-w