Dendritic cells dictate responses to PD-L1 blockade cancer immunotherapy.

Abstract

PD-L1/PD-1 blocking antibodies have demonstrated therapeutic efficacy across a range of human cancers. Extending this benefit to a greater number of patients, however, will require a better understanding of how these therapies instigate anticancer immunity. Although the PD-L1/PD-1 axis is typically associated with T cell function, we demonstrate here that dendritic cells (DCs) are an important target of PD-L1 blocking antibody. PD-L1 binds two receptors, PD-1 and B7.1 (CD80). PD-L1 is expressed much more abundantly than B7.1 on peripheral and tumor-associated DCs in patients with cancer. Blocking PD-L1 on DCs relieves B7.1 sequestration in cis by PD-L1, which allows the B7.1/CD28 interaction to enhance T cell priming. In line with this, in patients with renal cell carcinoma or non-small cell lung cancer treated with atezolizumab (PD-L1 blockade), a DC gene signature is strongly associated with improved overall survival. These data suggest that PD-L1 blockade reinvigorates DC function to generate potent anticancer T cell immunity.

• Authors: Maud Mayoux, Andreas Roller, Vesna Pulko, Stefano Sammicheli, Stanford Chen, Eva Sum, Christian Jost, Marieke F Fransen, Regula B Buser, Marcin Kowanetz, Karolin Rommel, Ines Matos, Sara Colombetti, Anton Belousov, Vaios Karanikas, Ferry Ossendorp, Priti S Hegde, Daniel S Chen, Pablo Umana, Mario Perro, Christian Klein, Wei Xu
• Journal: Science translational medicine (Sci Transl Med) Vol. 12 Issue 534 (03 11 2020) ISSN: 1946-6242 [Electronic] United States
• PMID: 32161104 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Chemical References

• Antibodies, Monoclonal, Humanized
• B7-H1 Antigen
• atezolizumab

Topics

• Antibodies, Monoclonal, Humanized (therapeutic use)
• B7-H1 Antigen (antagonists & inhibitors)
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Dendritic Cells
• Humans
• Immunotherapy
• Lung Neoplasms (drug therapy)