Regulatory Mechanisms of Inhibitory Immune Checkpoint Receptors Expression

Nicolas Curdy (1) , Olivia Lanvin (1) , Camille Laurent (2, 1) , Jean-Jacques Fournié (1) , Don-Marc Franchini (3)

1 CRCT - Centre de Recherches en Cancérologie de Toulouse
2 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
3 CIML - Centre d'Immunologie de Marseille - Luminy

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.

Mots clés: T cells; antitumor immunity; exhaustion; immune checkpoint; immunotherapy

Domaines: Immunologie

Nicolas Curdy, Olivia Lanvin, Camille Laurent, Jean-Jacques Fournié, Don-Marc Franchini. Regulatory Mechanisms of Inhibitory Immune Checkpoint Receptors Expression. Trends in Cell Biology, 2019, 29 (10), pp.777-790. ⟨10.1016/j.tcb.2019.07.002⟩. ⟨hal-02347417⟩