PD-L1 Testing and Immunotherapy: What Does It Mean?

PD-L1 testing is a biomarker test that can help doctors determine whether certain cancer patients may be candidates for particular immunotherapy treatments. It looks for a protein called PD-L1, which can be present on cancer cells and certain immune cells.

PD-L1 is part of the PD-1/PD-L1 immune checkpoint pathway. When PD-L1 binds to PD-1 on T cells, it can reduce the T cell's ability to attack the cancer. Some immunotherapy medicines block this pathway, helping T cells remain active against cancer.

If you are learning how this test fits into cancer treatment, it is also useful to understand the broader role of immunotherapy. Our Cancer Immunotherapy page provides an overview of how these treatments work and the different types of immunotherapy used in cancer care.

What Is PD-L1?

PD-L1 stands for programmed death-ligand 1. It is a protein involved in regulating the immune response. PD-L1 can be found on some normal cells and on certain cancer cells. When PD-L1 interacts with PD-1, a protein found on T cells, it can send an inhibitory signal that reduces T-cell activity.

This is normally one of the body's ways of preventing excessive immune activity. However, some cancer cells can use the PD-1/PD-L1 pathway to avoid being attacked by the immune system.

Immune checkpoint inhibitors can interfere with this interaction. By blocking PD-1 or PD-L1, they may allow T cells to remain more active against cancer cells.

What Is PD-L1 Testing?

PD-L1 testing is a laboratory test used to determine whether PD-L1 is present in a tumor and, depending on the cancer and test, how much is present.

The test is generally performed on a sample of cancer tissue obtained during a biopsy or surgery. A laboratory uses a technique called immunohistochemistry (IHC) to identify PD-L1 protein in the tissue.

The result is then reported using a scoring system. The scoring method depends on the type of cancer and the particular immunotherapy being considered.

Why Is PD-L1 Testing Done?

PD-L1 testing can help doctors decide whether a particular immunotherapy may be appropriate in certain cancer treatment settings.

Some immunotherapy medicines have specific indications based partly on PD-L1 expression. In these situations, the test can provide information that helps guide treatment selection.

However, PD-L1 testing is not a simple test that tells you whether immunotherapy will definitely work. A person's treatment plan depends on several factors, including the type and stage of cancer, other tumor biomarkers, previous treatments, overall health, and the specific immunotherapy being considered.

How Is a PD-L1 Test Performed?

PD-L1 testing generally uses tumor tissue that has already been collected for diagnosis or surgery. The basic process involves:

1. A tissue sample is obtained through a biopsy or surgery.
2. The sample is preserved and prepared for laboratory examination.
3. An immunohistochemical stain is used to identify PD-L1 protein.
4. A pathologist or trained laboratory professional evaluates the staining.
5. The result is reported using the scoring system appropriate for that cancer and test.

Because different tests and scoring systems are used, a PD-L1 result should always be interpreted in the context of the specific cancer and treatment being considered.

What Does PD-L1 TPS Mean?

Tumor Proportion Score (TPS) is one way of reporting PD-L1 expression. TPS represents the percentage of viable tumor cells showing PD-L1 staining. In simple terms, it estimates how many of the cancer cells in the tested sample show PD-L1 expression.

For example, a TPS of 50% means that approximately 50% of the viable tumor cells evaluated showed the relevant PD-L1 staining pattern.

TPS is used in certain cancers, particularly in some cases of non-small cell lung cancer (NSCLC). The cutoff used to guide treatment depends on the specific cancer, immunotherapy, and clinical indication.

What Does PD-L1 CPS Mean?

Combined Positive Score (CPS) is another way of assessing PD-L1 expression. Unlike TPS, CPS does not look only at tumor cells. It takes into account PD-L1-positive tumor cells as well as certain PD-L1-positive immune cells, such as lymphocytes and macrophages, in relation to the number of viable tumor cells.

The basic calculation is: CPS = Number of PD-L1-positive cells ÷ total number of viable tumor cells × 100

CPS is used in several cancer types and treatment settings. For example, it may be used in certain cases of gastric or gastroesophageal junction cancer, cervical cancer, head and neck cancer, urothelial cancer, and other cancers depending on the specific treatment indication.

This is why a CPS and a TPS should not be treated as interchangeable numbers. They measure PD-L1 expression differently.

Is a Higher PD-L1 Score Always Better?

No. A higher PD-L1 score does not simply mean that the cancer is “better” or “worse,” and it does not guarantee that immunotherapy will work. The meaning of a particular score depends on:

• The type of cancer
• The immunotherapy being considered
• The scoring method used
• The treatment indication
• Other biomarkers and characteristics of the tumor
• The patient's previous treatment and overall clinical situation

For some treatment decisions, a particular PD-L1 threshold may be used to identify patients who are eligible for an immunotherapy. In other situations, treatment may be possible even when PD-L1 expression is low or absent.

Why Can PD-L1 Results Differ Between Tests?

PD-L1 testing is not based on one universal laboratory test or one scoring system. Different assays can use different antibodies, laboratory methods, scoring approaches, and thresholds. 

The clinical significance of the result also depends on the specific cancer and treatment. This means that a PD-L1 score should not be interpreted in isolation or compared casually with a result obtained using a different test.

What Other Biomarkers Can Matter for Immunotherapy?

PD-L1 is only one biomarker that can influence immunotherapy decisions. Depending on the cancer, doctors may also consider characteristics such as:

• Microsatellite instability-high (MSI-H)
• Mismatch repair deficiency (dMMR)
• Other tumor-specific molecular alterations
• The overall immune and molecular characteristics of the tumor

Not every test is necessary for every patient. The appropriate biomarker testing depends on the cancer type and the treatment options under consideration.

The Bottom Line

PD-L1 testing helps doctors understand whether a tumor expresses the PD-L1 protein, which is involved in the immune checkpoint pathway targeted by several immunotherapy medicines.

The result may be reported using TPS, CPS, or another method depending on the cancer and test. A positive result can support the use of certain immunotherapies in specific treatment settings, but it does not guarantee that treatment will work. Similarly, a negative result does not automatically rule out every form of immunotherapy.

PD-L1 is therefore best viewed as one part of the overall treatment decision, rather than a standalone test that determines whether immunotherapy will succeed. The result needs to be interpreted alongside the cancer type, stage, other biomarkers, previous treatments, and the specific immunotherapy being considered.