Programmed cell death-1 and its ligands: Current knowledge and possibilities in immunotherapy

• Autor(a) principal: Gutic, Bojana
• Data de Publicação: 2023
• Outros Autores: Bozanovic, Tatjana, Mandic, Aljosa, Dugalic, Stefan, Todorovic, Jovana, Stanisavljevic, Dejana, Dugalic, Miroslava Gojnic, Sengul, Demet, Detanac, Dzenana A., Sengul, Ilker, Detanac, Dzemail, Soares Junior, José Maria
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Clinics
• Texto Completo: https://www.revistas.usp.br/clinics/article/view/214054
• topic: Programmed cell death; Ligands; Immunohistochemistry; Immunology; Pathology

Programmed Cell Death-1 (PCD-1) is a key immune checkpoint receptor, which mainly expresses on activated T, B, Dendritic (DC), Natural Killer (NK), and Treg cells. On the surface of activated T-cells, PCD-1 expression is upregulated after the recognition of peripherals antigens by T cells; subsequently, the elevated binding of PD-1 to Programmed Death Ligand-1 (PD-L1) and Programmed Death Ligand-2 (PD-L2) becomes a key step for downstream inhibitory signaling. Although the role of PD-L1 has been evaluated more thoroughly by clinical research, and PD-L1 has also been used more widely in the clinical setting, PD-L2 also plays an important role in the negative regulation of T-cells, one of the necessary conditions that lead to immune tolerance. Expression of PD-L1 either in tumors or in infiltrating immune cells has been verified predominantly by Immunohistochemistry (IHC) in a variety of tumors, suggesting a role for the PD-1/PD-L1 axis as a prognostic trait and therapeutic target across multiple histotypes. The complex interplay between these factors plays a major role in the diffusion and clinical application of PD-L1 IHC assays as predictive biomarkers of response to PD-1/PD-L1 inhibitors. Checkpoint blockades are registered for the treatment of various cancers, including gynecological malignancies.