%0 Journal Article
%T PD-L1 on host cells is essential for PD-L1 blockade每mediated tumor regression
%A Aditi Mulgaonkar
%A Guiyang Hao
%A Haidong Dong
%A Haidong Tang
%A Hua Peng
%A Janis M. Taube
%A Jian Qiao
%A Jingya Guo
%A Kien Nham
%A Mingyi Chen
%A Raquibul Hannan
%A Robert A. Anders
%A Susan M. Harrington
%A William Silvers
%A Xiangyan Qiu
%A Xiankai Sun
%A Xin Liu
%A Yahong Xiong
%A Yang-Xin Fu
%A Yangchun Xin
%A Yong Liang
%J The Journal of Clinical Investigation
%D 2018
%R 10.1172/JCI96061
%X Programmed death每ligand 1 (PD-L1) expression on tumor cells is essential for T cell impairment, and PD-L1 blockade therapy has shown unprecedented durable responses in several clinical studies. Although higher expression of PD-L1 on tumor cells is associated with a better immune response after Ab blockade, some PD-L1每negative patients also respond to this therapy. In the current study, we explored whether PD-L1 on tumor or host cells was essential for anti每PD-L1每mediated therapy in 2 different murine tumor models. Using real-time imaging in whole tumor tissues, we found that anti每PD-L1 Ab accumulates in tumor tissues, regardless of the status of PD-L1 expression on tumor cells. We further observed that, while PD-L1 on tumor cells was largely dispensable for the response to checkpoint blockade, PD-L1 in host myeloid cells was essential for this response. Additionally, PD-L1 signaling in defined antigen-presenting cells (APCs) negatively regulated and inhibited T cell activation. PD-L1 blockade inside tumors was not sufficient to mediate regression, as limiting T cell trafficking reduced the efficacy of the blockade. Together, these findings demonstrate that PD-L1 expressed in APCs, rather than on tumor cells, plays an essential role in checkpoint blockade therapy, providing an insight into the mechanisms of this therapy
%U https://www.jci.org/articles/view/96061