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

Front Immunol. 2018 Nov 27:9:2737. doi: 10.3389/fimmu.2018.02737. eCollection 2018.

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 humanized antibody to CTLA-4 was first approved clinically followed by the use of antibody blockade against PD-1 and its ligand PD-L1. Effective anti-tumor immunity requires the activation of tumor-specific effector T-cells, the blockade of regulatory cells and the migration of T-cells into the tumor. Here, we review data implicating CTLA-4 and PD-1 in the motility of T-cells with a specific reference to the potential exploitation of these pathways for more effective tumor infiltration and eradication.

Keywords: CTLA4; PD1; T-cell; cancer; check-point blockade; immune surveillance; migration; motility.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antibodies, Blocking / immunology
  • Antibodies, Monoclonal / immunology
  • Autoimmunity / immunology
  • CTLA-4 Antigen / immunology*
  • Cell Movement / immunology*
  • Humans
  • Immunotherapy / methods
  • Neoplasms / immunology*
  • Neoplasms / therapy*
  • Programmed Cell Death 1 Receptor / immunology*
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • Antibodies, Blocking
  • Antibodies, Monoclonal
  • CTLA-4 Antigen
  • Programmed Cell Death 1 Receptor