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

Guohao Wang, Lisi Xie, Bei Li, Wei Sang, Jie Yan, Jie Li, Hao Tian, Wenxi Li, Zhan Zhang, Ye Tian and Yunlu Dai ()
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Guohao Wang: University of Macau
Lisi Xie: University of Macau
Bei Li: University of Macau
Wei Sang: University of Macau
Jie Yan: University of Macau
Jie Li: University of Macau
Hao Tian: University of Macau
Wenxi Li: University of Macau
Zhan Zhang: University of Macau
Ye Tian: University of Macau
Yunlu Dai: University of Macau

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: 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 (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.

Date: 2021
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DOI: 10.1038/s41467-021-25990-w

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