TY - JOUR
T1 - PD-L1 on dendritic cells attenuates T cell activation and regulates response to immune checkpoint blockade
AU - Peng, Qi
AU - Qiu, Xiangyan
AU - Zhang, Zihan
AU - Zhang, Silin
AU - Zhang, Yuanyuan
AU - Liang, Yong
AU - Guo, Jingya
AU - Peng, Hua
AU - Chen, Mingyi
AU - Fu, Yang Xin
AU - Tang, Haidong
N1 - Funding Information:
We thank Dr. Wenxin Zheng for helpful scientific discussions. We thank services provided by the Laboratory Animal Research Center and Flow Cytometry Facility of Tsinghua University. This study was supported by Tsinghua-Peking University Center for Life Sciences (045-61020100119), Start-up Foundation of Tsinghua University (53332201119), and Foshan-Tsinghua Innovation Special Fund (FTISF, 041522068) to H.T.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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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U2 - 10.1038/s41467-020-18570-x
DO - 10.1038/s41467-020-18570-x
M3 - Article
C2 - 32973173
AN - SCOPUS:85091438813
SN - 2041-1723
VL - 11
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 4835
ER -