Negative immune checkpoints on T lymphocytes and their relevance to cancer immunotherapy

Mol Oncol. 2015 Dec;9(10):1936-65. doi: 10.1016/j.molonc.2015.10.008. Epub 2015 Oct 26.


The term 'inhibitory checkpoint' refers to the broad spectrum of co-receptors expressed by T cells that negatively regulate T cell activation thus playing a crucial role in maintaining peripheral self-tolerance. Co-inhibitory receptor ligands are highly expressed by a variety of malignancies allowing evasion of anti-tumour immunity. Recent studies demonstrate that manipulation of these co-inhibitory pathways can remove the immunological brakes that impede endogenous immune responses against tumours. Antibodies that block the interactions between co-inhibitory receptors and their ligands have delivered very promising clinical responses, as has been shown by recent successful trials targeting the CTLA-4 and PD-1 pathways. In this review, we discuss the mechanisms of action and expression pattern of co-inhibitory receptors on different T cells subsets, emphasising differences between CD4(+) and CD8(+) T cells. We also summarise recent clinical findings utilising immune checkpoint blockade.

Keywords: CTLA-4; Cancer immunotherapy; Inhibitory checkpoints; Inhibitory receptors on T cells; PD-1.

Publication types

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

MeSH terms

  • Animals
  • Humans
  • Immunotherapy*
  • Neoplasms / therapy*
  • T-Lymphocytes / immunology*