Interference with PD-L1/PD-1 co-stimulation results in effective anti-tumour immunity by preventing ligand-induced T cell receptor

D. Escors, T. Liechtenstein, N. Perez-Janices, A. Lanna, C. Bricogne, K. Karwaca, D. Guerrero-Setas, Karine Breckpot

Onderzoeksoutput: Conference paper

16 Citaten (Scopus)

Samenvatting

T cell receptor (TCR) down-modulation after antigen presentation is a fundamental process that regulates TCR signal transduction. Current understanding of this process is that intrinsic TCR/CD28 signal transduction leads to TCR down-modulation. We demonstrate a novel mechanism whereby the interaction between programmed cell death 1 ligand 1 (PD-L1) on dendritic cells (DCs) and programmed death 1 (PD-1) on CD8 T cells triggers ligand-induced TCR down-modulation. This occurred via Cbl-b E3 up-regulation in CD8 T cells. PD-L1 silencing in DCs with lentiviral vectors delivering microRNAs markedly inhibited TCR down-modulation. PD-L1 silencing hyper-activated CD8 T cells as assessed in vitro and in vivo in an arthritis model. Antitumour immune responses (lymphoma and melanoma) were accelerated and DC anti-tumour capacities potentiated, when combined with mitogen-activated kinase (MAPK) modulators that promote DC activation, or with cytokine priming.
Originele taal-2English
Pagina's (van-tot)170-170
TijdschriftHuman Gene Therapy
Volume24
Nummer van het tijdschrift12
StatusPublished - 1 dec 2013
EvenementThe European Society for Gene and Cell Therapy and the Spanish Society for Gene and Cell Therapy Collaborative Congress 2013 - Madrid, Spain
Duur: 25 okt 201328 okt 2013

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