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

Research output: Contribution to journalConference paper

16 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)170-170
JournalHuman Gene Therapy
Volume24
Issue number12
Publication statusPublished - 1 Dec 2013
EventThe European Society for Gene and Cell Therapy and the Spanish Society for Gene and Cell Therapy Collaborative Congress 2013 - Madrid, Spain
Duration: 25 Oct 201328 Oct 2013

Keywords

  • PD-L1/PD-1
  • T cell
  • tumour
  • tumor
  • ligand

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