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PD-L1 on dendritic cells attenuates T cell activation and regulates response to immune checkpoint blockade, Nat Commun, 24 Sep 2020

Updated: 2020-09-24

Nature Communications, 24 September, 2020, DOI:https://doi.org/10.1038/s41467-020-18570-x

 

PD-L1 on dendritic cells attenuates T cell activation and regulates response to immune checkpoint blockade


Qi Peng, Xiangyan Qiu, Zihan Zhang, Silin Zhang, Yuanyuan Zhang, Yong Liang, Jingya Guo, Hua Peng, Mingyi Chen, Yang-Xin Fu & Haidong Tang

 

Abstract


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.

 

Article link:https://www.nature.com/articles/s41467-020-18570-x

 

 

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