AUTHOR=Brunner-Weinzierl Monika C. , Rudd Christopher E. 

TITLE=CTLA-4 and PD-1 Control of T-Cell Motility and Migration: Implications for Tumor Immunotherapy

JOURNAL=Frontiers in Immunology

VOLUME=Volume 9 - 2018

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.02737

DOI=10.3389/fimmu.2018.02737

ISSN=1664-3224

ABSTRACT=CTLA-4 is a co-receptor on T-cells that controls peripheral tolerance and the development of
autoimmunity. Immune check-point blockade (ICB) uses monoclonal antibodies (MAbs) to block
the binding of inhibitory receptors (IRs) to their natural ligands. A humanised antibody to CTLA-
4 [Ipilimumab] was first approved clinically followed by antibody blockade of PD-1 [Nivolumab
and Pembrolizumab] and its ligand PD-L1 [Atezolizumab](Baumeister et al., 2016; Okazaki et al.,
2013; Page et al., 2014; Sharma et al., 2011) The function and mechanisms of action of CTLA-4
involve cell intrinsic and cell extrinsic pathways. Effective anti-tumour immunity requires the
activation of tumour-specific effector T cells, the blockade of regulatory cells and the migration
of T-cells into the tumour. In this review, we review data implicating CTLA-4 and PD-1 in the
motility of T-cells with a specific reference to the potential exploitation of theses pathways for
more effective tumour infiltration and eradication.