Open AccessNegative immune checkpoints on T lymphocytes and their relevance to cancer immunotherapy
Author(s) -
Śledzińska Anna,
Menger Laurie,
Bergerhoff Katharina,
Peggs Karl S.,
Quezada Sergio A.
Publication year - 2015
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1016/j.molonc.2015.10.008
Subject(s) - immune system , immunotherapy , cancer immunotherapy , biology , immune checkpoint , receptor , inhibitory postsynaptic potential , cd8 , cancer research , immunology , t cell , microbiology and biotechnology , neuroscience , genetics
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.