Programmed Death-Ligand 1, or PD-L1, is a protein found on the surface of many different cells throughout the body. It plays a regulatory role in immune responses and is considered an “immune checkpoint” protein. Understanding PD-L1’s function is central to comprehending both normal biological processes and its implications in various health conditions.
Understanding PD-L1
PD-L1, also known as CD274 or B7-H1, is a protein located on the outer surface of various cell types, including healthy cells and some cancer cells. It acts as a “ligand,” binding to another specific protein called Programmed Death-1 (PD-1), found on the surface of immune cells known as T-cells. This interaction forms a key component of the PD-1/PD-L1 pathway, an immune checkpoint pathway.
PD-L1’s Normal Role in Immunity
The PD-1/PD-L1 pathway serves a normal function in maintaining the immune system’s balance. PD-L1 on healthy cells interacts with PD-1 on T-cells, which identify and eliminate threats. This binding acts like a “brake pedal” for the immune system, preventing T-cells from mistakenly attacking the body’s own healthy tissues. This mechanism helps establish self-tolerance, preventing autoimmune diseases and ensuring immune responses are appropriately regulated.
How Cancer Cells Use PD-L1
Cancer cells often exhibit increased PD-L1 on their surfaces, known as overexpression. This allows them to “hide” from the immune system’s T-cells, which are programmed to detect and destroy abnormal cells. When PD-L1 on cancer cells binds to PD-1 on T-cells, it deactivates these T-cells. This deactivation prevents T-cells from recognizing and attacking the cancer cells, which is a key mechanism for tumor growth and survival.
Targeting PD-L1 in Cancer Therapy
Understanding how cancer cells exploit PD-L1 led to the development of immunotherapies, a class of drugs called immune checkpoint inhibitors. These therapies block the interaction between PD-1 and PD-L1. By preventing PD-L1 on cancer cells from binding to PD-1 on T-cells, these drugs “release the brakes” on the T-cells, allowing them to reactivate. Once reactivated, T-cells can recognize and attack the cancer cells, allowing the body’s immune response to fight the tumor. This represents an advance in cancer treatment, enabling the immune system to fight the disease.
Testing for PD-L1
Testing for the level of PD-L1 on tumor cells is a standard practice in oncology to guide treatment decisions. This assessment involves obtaining a tissue sample from the tumor through a biopsy. The sample is then analyzed using a technique called immunohistochemistry (IHC) to determine PD-L1 expression. Results can help doctors predict whether a patient is likely to benefit from therapies that block the PD-1 or PD-L1 pathway. While PD-L1 expression is an important biomarker, it is one of several factors considered when making personalized treatment plans.