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Immune-checkpoint inhibitors for combating T-cell dysfunction in cancer

Authors Grywalska E, Pasiarski M, Góźdź S, Roliński J

Received 7 May 2018

Accepted for publication 14 August 2018

Published 4 October 2018 Volume 2018:11 Pages 6505—6524


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Editor who approved publication: Dr Federico Perche

Ewelina Grywalska,1 Marcin Pasiarski,2,3 Stanisław Góźdź,3,4 Jacek Roliński1

1Department of Clinical Immunology and Immunotherapy, Medical University of Lublin, Lublin, Poland; 2Department of Hematology, Holy Cross Oncology Center of Kielce, Kielce, Poland; 3Faculty of Health Sciences, Jan Kochanowski University, Kielce, Poland; 4Department of Oncology, Holy Cross Oncology Center of Kielce, Kielce, Poland

Abstract: Under normal conditions, the immune system responds effectively to both external and internal threats without damaging healthy tissues. Cells undergoing a neoplastic transformation are one such threat. An efficient activation of T cells is enabled by T-cell receptor (TCR) interactions with antigen-presenting class I and class II molecules of the major histocompatibility complex (MHC), co-stimulatory molecules, and cytokines. After threatening stimuli are removed from the body, the host’s immune response ceases, which prevents tissue damage or chronic inflammation. The recognition of foreign antigens is highly selective, which requires multistep regulation to avoid reactions against the antigens of healthy cells. This multistep regulation includes central and peripheral tolerance toward the body’s own antigens. Here, we discuss T-cell dysfunction, which leads to poor effector function against foreign antigens, including cancer. We describe selected cellular receptors implicated in T-cell dysfunction and discuss how immune-checkpoint inhibitors can help overcome T-cell dysfunction in cancer treatment.

Keywords: B- and T-cell lymphocyte attenuator, cytotoxic T-cell antigen 4, lymphocyte-activation gene 3, programmed cell death protein 1, T-cell exhaustion, T-cell immunoglobulin and mucin domain 3, checkpoint inhibitors

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