Dendritic cells dictate responses to PD-L1 blockade cancer immunotherapy

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...

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Bibliographic Details
Published in:Science translational medicine 2020-03, Vol.12 (534), p.1
Main Authors: Mayoux, Maud, Roller, Andreas, Pulko, Vesna, Sammicheli, Stefano, Chen, Stanford, Sum, Eva, Jost, Christian, Fransen, Marieke F, Buser, Regula B, Kowanetz, Marcin, Rommel, Karolin, Matos, Ines, Colombetti, Sara, Belousov, Anton, Karanikas, Vaios, Ossendorp, Ferry, Hegde, Priti S, Chen, Daniel S, Umana, Pablo, Perro, Mario, Klein, Christian, Xu, Wei
Format: Article
Language:English
Subjects:
Antibodies, Monoclonal, Humanized - therapeutic use
B7 antigen
B7-H1 Antigen - antagonists & inhibitors
Blocking antibodies
Cancer immunotherapy
Carcinoma, Non-Small-Cell Lung - drug therapy
CD28 antigen
CD80 antigen
Dendritic Cells
Humans
Immunotherapy
Lung Neoplasms - drug therapy
Lymphocytes T
Monoclonal antibodies
Non-small cell lung carcinoma
PD-1 protein
PD-L1 protein
Renal cell carcinoma
Targeted cancer therapy
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Summary: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.
ISSN:1946-6234
1946-6242
1946-3242
DOI:10.1126/scitranslmed.aav7431