Dendritic cells dictate responses to PD-L1 blockade cancer immunotherapy.
Maud MayouxAndreas RollerVesna PulkoStefano SammicheliStanford ChenEva SumChristian JostMarieke F FransenRegula B BuserMarcin KowanetzKarolin RommelInes MatosSara ColombettiAnton BelousovVaios KaranikasFerry OssendorpPriti S HegdeDaniel C ChenPablo UmañaMario PerroChristiane NeumannWei XuPublished in: Science translational medicine (2021)
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.
Keyphrases
- dendritic cells
- immune response
- regulatory t cells
- end stage renal disease
- renal cell carcinoma
- newly diagnosed
- endothelial cells
- chronic kidney disease
- ejection fraction
- prognostic factors
- copy number
- induced pluripotent stem cells
- patient reported outcomes
- gene expression
- transcription factor
- patient reported
- young adults
- dna methylation
- deep learning
- pluripotent stem cells
- genome wide identification