Clinical Pharmacology and Interplay of Immune Checkpoint Agents: A Yin-Yang Balance

Arthur Geraud, Paul Gougis, Aurore Vozy, Celine Anquetil, Yves Allenbach, Emanuela Romano, Elisa Funck-Brentano, Javid J. Moslehi, Douglas B. Johnson, Joe Elie Salem

Résultats de recherche: Contribution à un journalArticle 'review'Revue par des pairs

58 Citations (Scopus)

Résumé

T cells have a central role in immune system balance. When activated, they may lead to autoimmune diseases. When too anergic, they contribute to infection spread and cancer proliferation. Immune checkpoint proteins regulate T cell function, including cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed cell death-1 (PD-1) and its ligand (PD-L1). These nodes of self-tolerance may be exploited pharmacologically to downregulate (CTLA-4 agonists) and activate CTLA-4 and PD-1/PD-L1 antagonists, also called immune checkpoint inhibitors (ICIs) the immune system.CTLA-4 agonists are used to treat rheumatologic immune disorders and graft rejection. CTLA-4, PD-1, and PD-L1 antagonists are approved for multiple cancer types and are being investigated for chronic viral infections. Notably, ICIs may be associated with immune-related adverse events (irAEs), which can be highly morbid or fatal. CTLA-4 agonism has been a promising method to reverse such life-threatening irAEs. Herein, we review the clinical pharmacology of these immune checkpoint agents with a focus on their interplay in human diseases.

langue originaleAnglais
Pages (de - à)85-112
Nombre de pages28
journalAnnual Review of Pharmacology and Toxicology
Volume61
Les DOIs
étatPublié - 6 janv. 2021
Modification externeOui

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