PD-L1 on dendritic cells attenuates T cell activation and regulates response to immune checkpoint blockade
Description
<jats:title>Abstract</jats:title><jats:p>Immune checkpoint blockade therapies have shown clinical promise in a variety of cancers, but how tumor-infiltrating T cells are activated remains unclear. In this study, we explore the functions of PD-L1 on dendritic cells (DCs), which highly express PD-L1. We observe that PD-L1 on DC plays a critical role in limiting T cell responses. Type 1 conventional DCs are essential for PD-L1 blockade and they upregulate PD-L1 upon antigen uptake. Upregulation of PD-L1 on DC is mediated by type II interferon. While DCs are the major antigen presenting cells for cross-presenting tumor antigens to T cells, subsequent PD-L1 upregulation protects them from killing by cytotoxic T lymphocytes, yet dampens the antitumor responses. Blocking PD-L1 in established tumors promotes re-activation of tumor-infiltrating T cells for tumor control. Our study identifies a critical and dynamic role of PD-L1 on DC, which needs to be harnessed for better invigoration of antitumor immune responses.</jats:p>
Journal
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- Nature Communications
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Nature Communications 11 (1), 4835-, 2020-09-24
Springer Science and Business Media LLC
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Details 詳細情報について
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- CRID
- 1360294647293310720
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- ISSN
- 20411723
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- Data Source
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- Crossref