Inhibitory immune checkpoint receptor (ICR) (ICR)

Inhibitory immune checkpoints and receptors are a diverse group of cell surface molecules that play a critical role in maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses (Pardoll, 2012, Nature Reviews Cancer). Under normal conditions, these receptors, such as Programmed cell death protein 1 (PD-1) and Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), act as "brakes" to prevent overactivation of the immune system and subsequent tissue damage (Ribas & Wolchok, 2018, Science). However, many tumors exploit these pathways by upregulating checkpoint ligands, thereby evading immune surveillance and inducing T-cell exhaustion (Sharma & Allison, 2015, Cell). Therapeutic intervention typically involves monoclonal antibodies known as checkpoint inhibitors, which block these inhibitory interactions to reinvigorate the host's anti-tumor immune response (Topalian et al., 2012, NEJM). While highly effective in various malignancies, targeting these receptors can lead to immune-related adverse events (irAEs) due to the systemic loss of immune suppression (Postow et al., 2018, NEJM). These receptors are now central to the standard of care in oncology, with ongoing research focusing on novel targets like Lymphocyte-activation gene 3 (LAG-3) and T-cell immunoreceptor with Ig and ITIM domains (TIGIT) (Andrews et al., 2017, Immunological Reviews). Beyond oncology, these pathways are being explored for their potential in treating chronic viral infections where T-cell exhaustion is a hallmark (Wykes & Lewin, 2018, Nature Reviews Immunology).

Other names

Immune checkpointCo-inhibitory receptorNegative immune regulatorCheckpoint proteinImmune checkpoint molecule

Monoclonal antibodies bind to inhibitory receptors or their ligands to block suppressive signaling pathways, thereby restoring the effector function of exhausted T-cells and enhancing anti-tumor immunity (Pardoll, 2012, Nature Reviews Cancer).