What is PD-L1?


PD-L1 (Programmed Death-Ligand 1) is a protein found on the surface of many normal cells and certain cancer cells. It is part of a natural system in the body called an immune checkpoint, which helps regulate your immune system and prevents it from becoming overactive. Specifically, PD-L1 interacts with another protein called PD-1, which is found on immune cells known as T cells. Normally, this interaction helps protect healthy cells from accidental damage by the immune system. However, some cancer cells take advantage of this mechanism by producing high levels of PD-L1, which helps them evade detection and attack by T cells. As a result, the cancer cells continue to grow and spread.

How do pathologists test for PD-L1?

Pathologists test for PD-L1 using a method called immunohistochemistry (IHC). For this test, a small sample of tumor tissue is collected and examined under a microscope. Special antibodies designed to attach specifically to PD-L1 are applied to the tissue. If PD-L1 is present, these antibodies will bind to it, causing the cells to appear colored (usually brown), clearly visible under the microscope.

The amount of PD-L1 expressed by the tumor cells and surrounding immune cells is then measured and reported using scoring systems that vary depending on the type of cancer:

  • Total Proportion Score (TPS): This scoring method is commonly used for lung cancer. TPS is calculated by determining the percentage of cancer cells that show PD-L1 staining. For example, a TPS of 50% means half of the cancer cells express PD-L1. A higher TPS indicates that the cancer cells have more PD-L1, which can help doctors determine if certain treatments, such as immunotherapy, may be effective.

  • Combined Positive Score (CPS): This scoring method is used for many other types of cancer, such as cancers of the stomach, esophagus, head and neck, bladder, and cervix. CPS measures PD-L1 expression on both cancer cells and immune cells surrounding the tumor. It is calculated by adding the number of PD-L1-positive cells (tumor and immune cells), dividing by the total number of tumor cells, and multiplying by 100. A higher CPS indicates a greater likelihood that the cancer may respond well to certain immune-based treatments.

Cancers with PD-L1

PD-L1 expression is frequently found in various cancers, especially those known for interacting closely with the immune system. These cancers commonly include:

  • Lung cancer, particularly non-small cell lung carcinoma (NSCLC)

  • Head and neck cancers, especially squamous cell carcinoma

  • Bladder cancer

  • Kidney (renal) cancer

  • Stomach and esophageal cancers

  • Liver cancer (hepatocellular carcinoma)

  • Ovarian cancer

  • Cervical cancer

  • Certain breast cancers, especially triple-negative breast cancer

  • Pancreatic cancer

  • Melanoma (skin cancer)

In these cancers, the presence of PD-L1 often indicates the cancer has developed ways to avoid detection by the immune system, helping the cancer cells survive, grow, and spread.

Treatments associated with PD-L1

Identifying PD-L1 in a tumor is important because it can help doctors choose specialized treatments known as immune checkpoint inhibitors. These therapies block the interaction between PD-1 and PD-L1, allowing the immune system to recognize and attack cancer cells effectively. Examples of immune checkpoint inhibitors include:

  • Pembrolizumab (Keytruda®)

  • Nivolumab (Opdivo®)

  • Atezolizumab (Tecentriq®)

  • Durvalumab (Imfinzi®)

  • Avelumab (Bavencio®)

Patients whose cancers test positive for PD-L1 often have a better chance of responding well to these treatments. Testing for PD-L1 helps ensure patients receive the most effective personalized therapy.

Why is PD-L1 important in a pathology report?

Testing for PD-L1 provides critical information that helps your healthcare team decide on the best treatment strategy. By understanding whether your cancer expresses PD-L1 and how strongly it does so (using TPS or CPS scoring), doctors can better predict how your cancer might respond to immunotherapy. This information ultimately helps to tailor your treatment, maximizing the chances of successfully controlling your cancer and improving outcomes.

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