Leiden University Scholarly Publications

Mayoux, M.; Roller, A.; Pulko, V.; Sammicheli, S.; Chen, S.; Sum, E.; ... ; Xu, W. (2020)

Dendritic cells dictate responses to PD-L1 blockade cancer immunotherapy

Article / Letter to editor

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...Show morePD-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.Show less

All authors

Mayoux, M.; Roller, A.; Pulko, V.; Sammicheli, S.; Chen, S.; Sum, E.; Jost, C.; Fransen, M.F.; Buser, R.B.; Kowanetz, M.; Rommel, K.; Matos, I.; Colombetti, S.; Belousov, A.; Karanikas, V.; Ossendorp, F.; Hegde, P.S.; Chen, D.S.; Umana, P.; Perro, M.; Klein, C.; Xu, W.

Date

2020-03-11

Journal

Science Translational Medicine

Volume

12

Issue

534

DOI

doi:10.1126/scitranslmed.aav7431