PD-L1 and Lung Cancer

The immune system plays an important role in protecting us from disease, it is the body’s way to fight infection and illness. The normal immune system generally recognizes the healthy cells and tries to detect and destroy what is unfamiliar. It destroys bacteria, viruses, and parasites. It is also involved in treating and preventing cancer.

How does immunotherapy work?

Immunotherapy is an anti-cancer treatment that harnesses the body’s immune system to prevent, control, treat, and destroy cancer. Also called biologic therapy, it is a kind of cancer treatment intended to boost a person’s natural defenses to fight cancer. Although it is not available or effective for all people and all diseases, there are certain types of immunotherapy that are considered effective.

Immune checkpoints and the immune system

Immune checkpoints regulate the activity of the immune system. They help to maintain homeostasis, a stable equilibrium of the immune system. These checkpoints signal the immune system so that T cells can recognize and attack tumors, and also prevent the immune system from attacking itself; called an autoimmune reaction.

Cancer cells can take over these checkpoints; protecting them so the immune system does not recognize them. This allows cancer cells to grow. By blocking the PD-1 checkpoint, the immune system can recognize cancer cells and destroy them.³

Immune checkpoint inhibitors

Immune checkpoints play a role in the anti-tumor immune response. Immune checkpoint inhibitors are cancer medications used to block the PD-1 protein. This means when PD-1 is blocked, T cells have an increased ability to fight cancer cells. Immune checkpoint inhibitors offer medical researchers and people with cancer continued hope for the future treatment of advanced lung cancers. PD-L1 protein expression has emerged as a biomarker that predicts which patients are more likely to respond to anti–PD-L1/PD-1 immunotherapy.

US Food and Drug Administration (FDA) approval of immunotherapies for advanced non-small cell lung cancer (NSCLC) has increased the treatment options and long-term prognosis for cancer patients.³ This type of therapy is sometimes called immune checkpoint blockade because it acts as a brake on immune cells -- the checkpoint -- it is blocked by the drug.²

What is PD-1?

PD-1 (programmed cell death protein-1) is an immune checkpoint protein found on cells in the human body.¹ It is present on immune T cells and works to keep them from attacking other healthy cells in the body. Its ligands, PD-L1 and PD-L2, also immune checkpoint proteins, are expressed on the surface of other cells. When PD-1 binds to PD-L1, it acts as a T-cell receptor signaling the T cells not to attack healthy cells. It tells the body to remain vigilant in defending against cancer.

Using therapies to target PD-1 or PD-L1

Some cancer cells have large amounts of PD-L1, which helps them hide from immune attack. Therapies that target either PD-1 or PD-L1 can stop them from attaching and help keep cancer cells from hiding.¹ The development of anti-PD-1/PD-L1 inhibitors for use in the treatment of advanced non-small cell lung cancer has significantly improved patient outcomes.²

Tumors can be positive or negative for surface PD-L1 protein expression with different clinical impact. Immunotherapy treatments can be used alone or in combination with surgery, chemotherapy, radiation, or targeted therapies to improve their effectiveness. PD-L1–negative tumors may still respond to anti–PD-1 or anti–PD-L1 therapy if given as part of a combination treatment which can get T cells into tumors.⁶

Conducting a pretreatment assessment of immune-related biomarkers including PD-L1 expression can help doctors review and select the best treatment approach for each person.^2,7