The PD-L1 gene is a segment of DNA that carries instructions for making the Programmed Death-Ligand 1 protein. This protein is found on the surface of various cells throughout the body. It plays a role in the immune system, helping to regulate its activity. Its function is particularly relevant in diseases like cancer.
The Role of PD-L1 in the Immune System
The PD-L1 protein functions as an “immune checkpoint,” maintaining balance within the immune system. When PD-L1 is present on healthy cells, it interacts with its partner protein, PD-1, found on immune cells called T-cells. This interaction acts like a “brake,” signaling T-cells not to attack healthy cells.
This interaction prevents the immune system from becoming overactive. By preventing T-cells from attacking healthy tissues, the PD-1/PD-L1 pathway contributes to immune tolerance. This helps avert autoimmune diseases, where the immune system mistakenly targets its own cells. The pathway ensures immune responses are controlled and do not cause unnecessary damage.
PD-L1 and Cancer’s Immune Evasion
Cancer cells often exploit the normal PD-L1 pathway to avoid immune detection and destruction. Many tumor cells produce high amounts of PD-L1 protein on their surface. This overexpression allows them to bind to PD-1 receptors on T-cells, effectively “turning off” T-cells, preventing them from eliminating cancer.
This mechanism allows tumors to escape immune surveillance, growing and spreading unchecked. Cancer cells use the body’s own immune regulatory system against itself, creating an immunosuppressive environment that protects the tumor. Increased PD-L1 expression can result from genetic alterations within tumor cells and inflammatory signals from the surrounding environment.
Targeting PD-L1 in Cancer Treatment
Understanding how cancer cells exploit the PD-L1 pathway has led to the development of immunotherapies. These therapies include “immune checkpoint inhibitors,” which block the interaction between PD-L1 (on cancer cells) and PD-1 (on T-cells). By interrupting this binding, these inhibitors “release the brakes” on T-cells, allowing them to reactivate and attack cancer cells.
These therapies restore the T-cells’ ability to mount an anti-tumor immune response. Immune checkpoint inhibitors have shown effectiveness across various cancer types, including melanoma, non-small cell lung cancer, renal cell carcinoma, and bladder cancer. This approach represents an advance in cancer treatment, offering new possibilities for patients with difficult-to-treat malignancies.
Testing for PD-L1 Expression
Testing for PD-L1 expression in tumor samples helps guide cancer treatment decisions. This testing is performed using immunohistochemistry (IHC). IHC uses antibodies that bind to the PD-L1 protein, allowing pathologists to visualize its presence on tumor cells.
The level of PD-L1 expression can serve as a “biomarker,” helping predict how likely a patient is to respond to PD-1/PD-L1 targeted immunotherapies. While higher PD-L1 expression on tumor cells often correlates with a better response, it is not an absolute predictor. Other factors are also considered, as the immune system’s interaction with cancer is complex, and responses can vary.