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

Q Peng, X Qiu, Z Zhang, S Zhang, Y Zhang… - Nature …, 2020 - nature.com
Q Peng, X Qiu, Z Zhang, S Zhang, Y Zhang, Y Liang, J Guo, H Peng, M Chen, YX Fu, H Tang
Nature communications, 2020nature.com
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 …
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.
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