PD-1 Blockade and CD27 Stimulation Activate Distinct Transcriptional Programs That Synergize for CD8⁺ T-Cell-Driven Antitumor Immunity.

ABSTRACT: Purpose: PD-1 checkpoint blockade has revolutionized the field of cancer immunotherapy, yet the frequency of responding patients is limited by inadequate T-cell priming secondary to a paucity of activatory dendritic cells (DC). DC signals can be bypassed by CD27 agonists, and we therefore investigated if the effectiveness of anti-PD-1/L1 could be improved by combining with agonist anti-CD27 monoclonal antibodies (mAb).Experimental Design: The efficacy of PD-1/L1 blockade or agonist anti-CD27 mAb was compared with a dual-therapy approach in multiple tumor models. Global transcriptional profiling and flow cytometry analysis were used to delineate mechanisms underpinning the observed synergy.Results: PD-1/PD-L1 blockade and agonist anti-CD27 mAb synergize for increased CD

SUBMITTER: Buchan SL 

PROVIDER: S-EPMC5959006 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature