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Article Dans Une Revue Annual Review of Pharmacology and Toxicology Année : 2021

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

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. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 61 is January 8, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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Dates et versions

hal-02949235 , version 1 (25-09-2020)

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Arthur Geraud, Paul Gougis, Aurore Vozy, Celine Anquetil, Yves Allenbach, et al.. Clinical Pharmacology and Interplay of Immune Checkpoint Agents: A Yin-Yang Balance. Annual Review of Pharmacology and Toxicology, 2021, 61 (1), ⟨10.1146/annurev-pharmtox-022820-093805⟩. ⟨hal-02949235⟩
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