Dendritic cells dictate responses to PD-L1 blockade cancer immunotherapy
Maud Mayoux, Andreas Roller, Vesna Pulko, Stefano Sammicheli, Stanford Chen, Eva Sum, Christian Jöst, 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 Umaña, Mario Perro, Christian Klein, Wei Xu
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.