If you have been assessed for pembrolizumab, your oncologist almost certainly discussed your PD-L1 expression. It is the single most important biomarker in determining whether you are a candidate for this treatment - but what does it actually mean, and how does it get measured?
What is PD-L1?
PD-L1 stands for Programmed Death-Ligand 1. It is a protein expressed on the surface of many cell types - including, importantly, the surface of many cancer cells. When PD-L1 binds to the PD-1 receptor on a T cell (a frontline immune cell), it sends an inhibitory signal: stand down, do not attack.
Tumours exploit this mechanism. By expressing PD-L1, they effectively tell patrolling immune cells that they are harmless, avoiding immune destruction. Pembrolizumab blocks this interaction by binding to PD-1, preventing PD-L1 from delivering its inhibitory message. The result is that T cells remain active and can target the tumour.
How is PD-L1 expression measured?
PD-L1 testing is performed through immunohistochemistry (IHC) - a laboratory technique applied to tumour tissue from a biopsy or surgical specimen. A pathologist uses a staining process to visualise PD-L1 protein on the tissue sample, then counts the proportion of cells that stain positive.
Two scoring systems are used, depending on the cancer type:
- Tumour Proportion Score (TPS): Used in lung cancer and some other tumour types. It measures the percentage of viable tumour cells that express PD-L1. A TPS of 50% or higher is considered "high expression" and often qualifies patients for pembrolizumab monotherapy.
- Combined Positive Score (CPS): Used in head and neck cancer, gastric cancer, cervical cancer, and others. It counts PD-L1-positive tumour cells, lymphocytes, and macrophages, divided by the total number of viable tumour cells. CPS thresholds of 1 and 20 are used in different clinical settings.
What does your score mean for treatment?
The relationship between PD-L1 score and treatment eligibility is not a simple on/off switch - it varies by cancer type and treatment line. In non-small cell lung cancer, the KEYNOTE-024 trial demonstrated that patients with TPS 50% or higher derived particularly strong benefit from pembrolizumab monotherapy as a first treatment. For patients with lower scores (1-49%), pembrolizumab in combination with chemotherapy may still be appropriate.
In head and neck cancer, a CPS of 1 or higher is required for some pembrolizumab indications, while a CPS of 20 or higher is required for others. The precise threshold depends on the specific approval and clinical context.
What if PD-L1 is low or absent?
A low or negative PD-L1 score does not necessarily rule out pembrolizumab. Some tumours are eligible regardless of PD-L1 status - particularly those with microsatellite instability-high (MSI-H) or mismatch repair deficiency (dMMR), which predict immunotherapy response through a different mechanism entirely. Additionally, pembrolizumab in combination with chemotherapy can benefit some patients with low PD-L1 expression.
The key takeaway is that PD-L1 expression is a starting point for eligibility assessment, not a complete answer. An experienced oncologist will interpret your result in the context of your cancer type, stage, overall health, and other biomarkers.
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