Title: Immune checkpoint inhibitors in cancer therapy


Authors: Eika S. Webb1, Peng Liu1, Renato Baleeiro1, Nicholas R. Lemoine1,2, Ming Yuan1, Yaohe Wang1,2


Institutions: 1Center for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, EC1M 6BQ, UK; 2Sino-British Research Centre for Molecular Oncology, National Center for International Research in Cell and Gene Therapy, Zhengzhou University, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450002, China.


Abstract: In recent years immune checkpoint inhibitors have garnered attention as being one of the most promising types of immunotherapy on the horizon. There has been particular focus on the immune checkpoint molecules, cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1) which have been shown to have potent immunomodulatory effects through their function as negative regulators of T cell activation. CTLA-4, through engagement with its ligands B7-1 (CD80) and B7-2 (CD86), plays a pivotal role in attenuating the activation of naïve and memory T cells. In contrast, PD-1 is primarily involved in modulating T cell activity in peripheral tissues via its interaction with PD-L1 and PD-L2. The discovery of these negative regulators of the immune response was crucial in the development of checkpoint inhibitors. This shifted the focus from developing therapies that targeted activation of the host immune system against cancer to checkpoint inhibitors, which aimed to mediate tumor cell destruction through the removal of coinhibitory signals blocking anti-tumor T cell responses.


Keywords: checkpoint inhibitor, CTLA-4, PD-1, immunotherapy, cancer


Full Text: JBR-2016-0168.pdf


J Biomed Res published on 15 May 2017, doi:10.7555/JBR.31.20160168