PD-L1 on host cells is essential for PD-L1 blockade-mediated tumor regression

J Clin Invest. 2018 Feb 1;128(2):580-588. doi: 10.1172/JCI96061. Epub 2018 Jan 16.


Programmed death-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-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-PD-L1-mediated therapy in 2 different murine tumor models. Using real-time imaging in whole tumor tissues, we found that anti-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.

Keywords: Cancer immunotherapy; Cellular immune response; Immunology; Oncology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antigen-Presenting Cells / immunology
  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / immunology*
  • Cell Line
  • Cell Line, Tumor
  • Flow Cytometry
  • Immunity, Cellular
  • Immunotherapy
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Myeloid Cells / metabolism
  • Neoplasms / immunology*
  • Neoplasms / therapy*
  • Tumor Microenvironment / immunology


  • Antibodies, Monoclonal
  • B7-H1 Antigen
  • CD274 protein, human