PD-L1 Expression — Immune Checkpoint Biomarker

Programmed death-ligand 1 (PD-L1) is a transmembrane protein that regularly acts as an immune checkpoint downregulator. In healthy physiology, it binds to the PD-1 receptor on T lymphocytes, preventing excessive immune activation and autoimmune tissue damage. Many malignant tumours exploit this pathway by overexpressing PD-L1, effectively disabling cytotoxic T cells and evading immune surveillance.

Pathologists evaluate PD-L1 expression through immunohistochemistry (IHC) performed on formal-fixed paraffin-embedded tissue specimens obtained via biopsy or surgery. Specific diagnostic assays calculate staining intensity and distribution, generating numerical metrics such as the tumour proportion score (TPS) or combined positive score (CPS).

Evaluating PD-L1 expression provides vital predictive insight that refines therapeutic decision-making. Knowing the score clarifies whether immune checkpoint inhibitors are appropriate as monotherapy, if they should be combined with chemotherapy, or if alternative systemic options should take precedence. This precision spares individuals from treatments unlikely to work and directs them toward regimens offering the highest biological rationale. It also informs clinical trial eligibility, opening doors to novel therapeutic combinations tailored to specific immune profiles.

PD-L1 status is evaluated via immunohistochemistry (IHC) on tumour tissue. Standardised commercial assays—such as 22C3, 28-8, and SP142—use monoclonal antibodies to stain the protein. Pathologists quantify results using scoring systems: Tumour Proportion Score (percentage of viable tumour cells showing membrane staining) or Combined Positive Score (which incorporates stained lymphocytes and macrophages). Results are often interpreted alongside mismatch repair (dMMR/MSI) and tumour mutational burden (TMB).

PD-L1 testing is most established in non-small cell lung cancer (NSCLC), where it guides frontline drug selection. It is also routinely evaluated in triple-negative breast cancer, urothelial (bladder) carcinoma, oesophageal adenocarcinoma, gastric cancer, cervical cancer, head and neck squamous cell carcinoma, and classical Hodgkin lymphoma. Expression thresholds and clinical utility vary significantly across these distinct tumour types.

High PD-L1 expression often indicates suitability for PD-1 inhibitors (such as pembrolizumab, nivolumab, or cemiplimab) or PD-L1 inhibitors (such as atezolizumab or durvalumab). In certain advanced lung cancers, high expression permits immunotherapy without cytotoxic chemotherapy. Low or negative scores do not entirely preclude immunotherapy, but typically require combination regimens featuring chemotherapy or dual checkpoint blockade.