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

Area of Science:

• Immunology
• Oncology
• Molecular Biology

Background:

• Programmed Cell Death-1 (PD-1) is a key immune checkpoint receptor expressed on various immune cells, including T cells, B cells, dendritic cells, NK cells, and Treg cells.
• PD-1 expression on activated T cells increases upon recognition of peripheral antigens, leading to T-cell inhibition through binding with Programmed Death Ligands (PD-L1 and PD-L2).
• While PD-L1 is widely studied and clinically utilized, PD-L2 also plays a significant role in T-cell regulation and immune tolerance.

Purpose of the Study:

• To elucidate the role of the PD-1/PD-L1 axis in cancer.
• To evaluate the clinical significance of PD-L1 expression as a prognostic and predictive biomarker.
• To understand the interplay of PD-1, PD-L1, and PD-L2 in the context of immune checkpoint inhibitors.

Main Methods:

• Review of clinical research and data focusing on PD-1/PD-L1 axis.
• Predominant use of Immunohistochemistry (IHC) to verify PD-L1 expression in tumors and infiltrating immune cells.
• Analysis of the clinical application of PD-L1 IHC assays as predictive biomarkers.

Main Results:

• PD-L1 expression in tumors and immune cells is a verified prognostic trait across multiple cancer types.
• The PD-1/PD-L1 axis is a significant therapeutic target in cancer treatment.
• The complex interactions involving PD-1, PD-L1, and PD-L2 influence the clinical utility of PD-L1 IHC assays.

Conclusions:

• The PD-1/PD-L1 axis is a critical regulator of immune responses and a validated target for cancer immunotherapy.
• PD-L1 IHC assays are crucial for predicting response to PD-1/PD-L1 inhibitors, despite complexities in their application.
• Checkpoint blockade therapies targeting the PD-1/PD-L1 pathway are effective in treating various cancers, including gynecological malignancies.