Ex vivo modelling of PD-1/PD-L1 immune checkpoint blockade under acute, chronic, and exhaustion-like conditions of T-cell stimulation.
Alexander Roberts, Lindsay Bentley, Tina Tang, Fay Stewart, Chiara Pallini, Joel Juvvanapudi, Graham R Wallace, Alison J Cooper, Aaron Scott, David Thickett, Sebastian T Lugg, Hollie Bancroft, Bridget Hemming, Charlotte Ferris, Gerald Langman, Andrew Robinson, Joanne Chapman, Babu Naidu, Thomas Pinkney, Graham S Taylor Show all
Scientific Reports | Published : 2021
Blockade of PD-1/PD-L1 interactions is proving an exciting, durable therapeutic modality in a range of cancers whereby T cells are released from checkpoint inhibition to revive their inherent anti-tumour activity. Here we have studied various ways to model ex vivo T cell function in order to compare the impact of the clinically utilised anti-PD-1 antibody, pembrolizumab (Keytruda) on the activation of human T cells: focussing on the release of pro-inflammatory IFNγ and anti-inflammatory IL-10 to assess functionality. Firstly, we investigated the actions of pembrolizumab in an acute model of T-cell activation with either immature or mature allogeneic dendritic cells (DCs); pembrolizumab enhan..View full abstract