A rheostat for immune responses: the unique properties of PD-1 and their advantages for clinical application

By Taku Okazaki, S. Chikuma, Yoshiko Iwai, S. Fagarasan, Tasuku Honjo. Nature Immunology, 2013

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Anti-NKG2A mAb Is a Checkpoint Inhibitor that Promotes Anti-tumor Immunity by Unleashing Both T and NK Cells (2018, background): “Immuno-oncology has revolutionized cancer treatment (Okazaki and Honjo, 2007; Okazaki et al., 2013; Baumeister et al., 2016; Schumacher and Schreiber, 2015; Sharma and Allison, 2015a, 2015b).”
Cancer immunotherapy: the beginning of the end of cancer? (2016, background): “cells, inhibits T cell proliferation, cytokine release, and cytotoxicity [81–83].”
Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Cervical Cancer: Results From the Phase II KEYNOTE-158 Study. (2019, background): “Programmed death-1 (PD-1) is a T-cell coinhibitory receptor that functions in an immunoregulatory capacity under normal conditions.(19) PD-1 plays a significant role in cancer by contributing to the ability of a tumor to evade immunosurveillance.”
Bioenergetic insufficiencies due to metabolic alterations regulated by PD-1 are an early driver of CD8+ T cell exhaustion (2016, background): “As a result, PD-1 can function asa rheostat to tuneTCRsignaling in tissuesduring infections (Honda et al., 2014;Okazaki et al., 2013).”
Nivolumab and Ipilimumab versus Ipilimumab in Untreated Melanoma (2015, background): “Increased lipase 12 (13) 8 (9) 2 (4) 1 (2)”