PD-L1 Testing in Cancer: What Your Score Means for Immunotherapy

The immune system relies on checkpoint proteins to avoid attacking the body's own healthy cells — a safeguard against autoimmune disease. PD-1 (programmed cell death protein 1) is a checkpoint receptor found on the surface of T cells, the immune cells responsible for recognising and killing abnormal cells. When PD-1 binds its partner protein, PD-L1, the T cell receives a signal to stand down rather than attack.

Many tumours exploit this normal safety mechanism. By expressing PD-L1 on the surface of cancer cells, or by inducing PD-L1 expression on nearby immune cells within the tumour microenvironment, a cancer can effectively present a 'do not attack' signal to approaching T cells, allowing it to grow despite an active immune system nearby. This is sometimes described as immune evasion or immune escape.

PD-1/PD-L1 inhibitor drugs — a subclass of immune checkpoint inhibitors — are antibodies designed to block either the PD-1 receptor on T cells or the PD-L1 protein on tumour or immune cells, physically preventing the two from binding. With the brake released, T cells already present around the tumour can resume recognising cancer cells as foreign and mount an attack. This mechanism is fundamentally different from chemotherapy, which kills dividing cells directly, or from targeted therapy, which blocks a specific growth-driving mutation; immunotherapy works by re-enabling the patient's own immune system.

If your report shows a PD-L1 score, what it means depends entirely on your cancer type and which drug is being considered, because thresholds are not universal. A TPS or CPS of, for example, 1 percent might be considered 'positive' for one drug and one cancer type but not for another. Ask your oncologist to explain the specific threshold that applies to your situation and which assay was used, since this affects which immunotherapy regimens you may be offered, sometimes in combination with chemotherapy rather than immunotherapy alone.

A low or negative PD-L1 result is not the same as 'immunotherapy will not work.' Some patients with low PD-L1 expression still respond meaningfully to checkpoint inhibitors, particularly when other factors such as high tumour mutational burden or MSI-high/mismatch repair deficient status are present, or when the drug is combined with chemotherapy. Conversely, a high score raises the probability of benefit but does not guarantee it. This is why PD-L1 is often described as an imperfect, or enriching, biomarker rather than a definitive gatekeeper: it shifts the odds rather than settling them. Understanding this nuance is part of what a broader guide to what cancer biomarkers are can help clarify, since predictive biomarkers generally describe probabilities rather than certainties.

PD-L1 testing is not used to diagnose cancer; it is performed after a cancer diagnosis has already been established, typically once the tumour type, stage and other relevant biomarkers are being assessed to plan systemic treatment. It is usually ordered alongside other molecular tests, such as gene mutation panels, MSI/mismatch repair status, or HER2 testing depending on the cancer type, so that oncologists have a complete biological picture before recommending a regimen. Results are typically available within one to two weeks, though this can vary by laboratory.

PD-L1 is measured by immunohistochemistry (IHC), a laboratory technique in which a thin slice of tumour tissue on a glass slide is stained with an antibody that binds specifically to the PD-L1 protein. A pathologist then examines the stained slide under a microscope and calculates a score based on the proportion and pattern of stained cells.

PD-L1 testing plays a role across several cancer types, each with its own approach to scoring and thresholds.

In non-small cell lung cancer (NSCLC), PD-L1 TPS is one of the most established biomarkers guiding first-line treatment choice: tumours with high PD-L1 expression may be candidates for checkpoint inhibitor monotherapy, while those with lower expression are more often treated with immunotherapy combined with chemotherapy.

In gastric and gastroesophageal junction cancer, PD-L1 CPS helps identify patients likely to benefit from adding a checkpoint inhibitor to first-line chemotherapy, with different CPS thresholds studied for different agents.

In head and neck squamous cell cancer, PD-L1 CPS is used to guide first-line treatment decisions in recurrent or metastatic disease, including whether immunotherapy can be used alone or should be combined with chemotherapy.

In urothelial (bladder) cancer, PD-L1 testing using IC or CPS scoring can inform first-line treatment choice, particularly for patients who are not considered fit for platinum-based chemotherapy.

In triple-negative breast cancer (TNBC), PD-L1 IC or CPS status helps determine whether a checkpoint inhibitor can be added to chemotherapy in the metastatic or early-stage (neoadjuvant) setting.

PD-L1 testing also has an emerging or established role in other cancers including melanoma, renal cell carcinoma, cervical cancer, hepatocellular carcinoma and Hodgkin lymphoma, though the strength of its predictive value differs across these settings.

Because PD-L1 expression can change over the course of disease — for instance after chemotherapy, radiotherapy, or as a tumour evolves and spreads — retesting on a newer sample is sometimes considered if treatment needs to be reconsidered, particularly if the original sample is old or if a new metastatic site has been biopsied. It is also worth knowing that PD-L1 status is only one input into an immunotherapy decision; oncologists weigh it alongside overall health, other biomarkers such as MSI-high/dMMR status and tumour mutational burden, prior treatments, and the option of enrolling in a clinical trial exploring newer checkpoint or combination approaches.

Immunotherapy brings a distinctive safety profile that differs from chemotherapy: because it activates the immune system broadly, it can occasionally cause the immune system to attack healthy tissue, producing immune-related side effects that may involve the skin, gut, lungs, liver, hormone-producing glands or other organs. These reactions are usually manageable when recognised early, often with corticosteroids or a pause in treatment, but they require prompt reporting of new symptoms to the care team, since delayed recognition can allow a mild reaction to become more serious.