Dendritic cells dictate responses to PD-L1 blockade cancer immunotherapy
| Autor: | Mario Perro, Vaios Karanikas, Marcin Kowanetz, Andreas Roller, Christian Klein, Marieke F. Fransen, Ines Matos, Stefano Sammicheli, Stanford Chen, Eva Sum, Pablo Umana, Vesna Pulko, Christian Jost, Regula B. Buser, Daniel S. Chen, Priti S. Hegde, Ferry Ossendorp, Sara Colombetti, Maud Léa Mayoux, Wei Xu, Anton Belousov, Karolin Rommel |
|---|---|
| Přispěvatelé: | Pulmonary medicine, CCA - Cancer biology and immunology |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Lung Neoplasms
biology business.industry medicine.medical_treatment T cell CD28 General Medicine Immunotherapy Dendritic Cells Antibodies Monoclonal Humanized B7-H1 Antigen medicine.anatomical_structure Cancer immunotherapy Atezolizumab PD-L1 Carcinoma Non-Small-Cell Lung Blocking antibody biology.protein Cancer research Medicine Humans business CD80 |
| Zdroj: | 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 2020, ' Dendritic cells dictate responses to PD-L1 blockade cancer immunotherapy ', Science Translational Medicine, vol. 12, no. 534, eaav7431 . https://doi.org/10.1126/scitranslmed.aav7431 Science Translational Medicine, 12(534):eaav7431. American Association for the Advancement of Science Science Translational Medicine, 12(534). AMER ASSOC ADVANCEMENT SCIENCE |
| ISSN: | 1946-6234 |
| DOI: | 10.1126/scitranslmed.aav7431 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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