Abstract
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.
Keywords:
Programmed cell death; Ligands; Immunohistochemistry; Immunology; Pathology
HIGHLIGHTS
Recently, cancer immunotherapy targeting PD-1 or PD-L1 has proven effective in causing durable antitumor immune responses with less toxicity in many types of tumors.
PD-1/PD-L1 blockade therapy will be the major cancer immunotherapy modality.
A deeper understanding of personal genomic information, and personalized markers in guiding anti-PD therapy.
Similar to the tip of an iceberg, PD-1/PD-L1 blockade antitumor immunotherapy opens a new era of cancer treatment, and further work on safety and efficiency will be required.