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The PD‐1 Interactome
Author(s) -
Wang Qi,
Bardhan Kankana,
Boussiotis Vassiliki A.,
Patsoukis Nikolaos
Publication year - 2021
Publication title -
advanced biology
Language(s) - English
Resource type - Journals
ISSN - 2701-0198
DOI - 10.1002/adbi.202100758
Subject(s) - interactome , immunotherapy , signal transduction , intracellular , peripheral tolerance , immune system , t cell , microbiology and biotechnology , cancer immunotherapy , cancer research , chemistry , biology , computational biology , neuroscience , immunology , biochemistry , gene
T cell activation is a fine‐tuned process that involves T cell receptor and costimulation signals. To prevent undue activation of T cells, inhibitory molecules including PD‐1 (programmed death 1) are induced and function as brakes for T cell signaling. In a steady state, the interaction of PD‐1 with its ligands PD‐L1 (B7‐H1, CD274) and PD‐L2 (B7‐DC, CD273) maintains peripheral immune tolerance. However, the expression of PD‐L1 on tumor cells and interaction with PD‐1 on T cells dampen anti‐tumor immunity. Therapeutic inhibitors of the PD‐1 pathway have revolutionized tumor immunotherapy. Unfortunately, the majority of patients do not develop sustained anti‐tumor responses. However, the knowledge about unique PD‐1 interactions and their role in mediating PD‐1 inhibitory signals is currently limited. Advances in the mechanistic understanding of the molecular and signaling integration of the PD‐1 pathway could unleash the great potential in tumor immunotherapy by allowing the development of combinatorial approaches that target not only PD‐1 and its ligands but also its unique downstream signal mediators. In this review, the current advances in understanding the mechanisms of extracellular and intracellular PD‐1 interactions and their significance in potential future therapeutic approaches are discussed.