title: PD-L1/PD-1 Co-Stimulation, a Brake for T cell Activation and a T cell Differentiation Signal.
abstract: For T cell activation, three signals have to be provided from the antigen presenting cell; Signal 1 (antigen recognition), signal 2 (co-stimulation) and signal 3 (cytokine priming). Blocking negative co-stimulation during antigen presentation to T cells is becoming a promising therapeutic strategy to enhance cancer immunotherapy. Here we will focus on interference with PD-1/PD-L1 negative co-stimulation during antigen presentation to T cells as a therapeutic approach. We will discuss the potential mechanisms and the therapeutic consequences by which interference/inhibition with this interaction results in anti-tumour immunity. Particularly, we will comment on whether blocking negative co-stimulation provides differentiation signals to T cells undergoing antigen presentation. A major dogma in immunology states that T cell differentiation signals are given by cytokines and chemokines (signal 3) rather than co-stimulation (signal 2). We will discuss whether this is the case when blocking PD-L1/PD-1 negative co-stimulation.
authors.affiliation: Division of Infection and Immunity, Rayne Institute, University College London, 5 University Street, WC1E 6JF, London, UK.
authors.forename: Therese
authors.initials: T
authors.lastname: Liechtenstein
authors.forename: Ines
authors.initials: I
authors.lastname: Dufait
authors.forename: Christopher
authors.initials: C
authors.lastname: Bricogne
authors.forename: Alessio
authors.initials: A
authors.lastname: Lanna
authors.forename: Joeri
authors.initials: J
authors.lastname: Pen
authors.forename: Karine
authors.initials: K
authors.lastname: Breckpot
authors.forename: David
authors.initials: D
authors.lastname: Escors
keywords: CD80; Cancer; Co-stimulation; Dendritic cell; Immunotherapy; PD-1; PD-L1