Regulatory Mechanisms of Inhibitory Immune Checkpoint Receptors Expression.

Trends Cell Biol

Cancer Research Center of Toulouse (CRCT), Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) 1037, Centre National de la Recherche Scientifique (CNRS) Equipe de Recherche Labellisée (ERL) 5294, 31037 Toulouse, France; Université Toulouse III Paul Sabatier, 31330 Toulouse, France; Institut Universitaire du Cancer de Toulouse-Oncopole, 31100 Toulouse, France. Electronic address:

Published: October 2019

T cells responding to persistent tumor or viral antigens progressively lose their functional properties, a feature known as exhaustion. This state is also characterized by cell-surface expression of multiple inhibitory immune checkpoint receptors (IRs). Cancer immunotherapy by immune checkpoint targeting has shown impressive clinical outcomes, but requires substantial improvement given the limited number of patients who benefit from the treatment. Targeting the mechanisms controlling immune checkpoint expression could represent a step towards this aim. Accumulating data indicate that this strategy can limit immune checkpoint expression, in some instances simultaneously inhibiting several immune checkpoints. This review discusses various mechanisms through which IRs are activated or regulated, and ways these mechanisms could be exploited to develop more effective future immunotherapies.

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http://dx.doi.org/10.1016/j.tcb.2019.07.002DOI Listing

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