OncoTargets and Therapy (Oct 2018)
Immune-checkpoint inhibitors for combating T-cell dysfunction in cancer
Abstract
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
