What Is PD-L1?
PD-L1 (Programmed Death-Ligand 1) is a protein found on the surface of cancer cells and immune cells. It acts as a "brake" on the immune system — when PD-L1 binds to PD-1 (a protein on T cells), it turns off the T cell, preventing it from attacking the cancer.
Cancer cells exploit this mechanism to hide from and suppress the immune response. Checkpoint inhibitor immunotherapy drugs — like pembrolizumab (Keytruda) and atezolizumab (Tecentriq) — work by blocking the PD-1/PD-L1 interaction, releasing the immune "brake" and allowing T cells to attack cancer.
Understanding PD-L1 Expression
PD-L1 expression is measured using a test called immunohistochemistry (IHC) on a tumor biopsy sample. Results are reported as a percentage of cancer cells expressing PD-L1:
- Negative: < 1% of cells express PD-L1
- Low positive: 1–49% expression
- High positive: ≥ 50% expression (called "high PD-L1 expression" or "TPS ≥ 50%")
How PD-L1 Affects Treatment Decisions
For non-small cell lung cancer (NSCLC): patients with TPS ≥ 50% may be eligible for pembrolizumab (Keytruda) as a first-line treatment instead of chemotherapy. For other cancers, PD-L1 expression may determine eligibility for specific immunotherapy drugs or combinations.
Important Limitations
PD-L1 expression is not a perfect predictor of immunotherapy response. Some patients with low or negative PD-L1 still respond to immunotherapy, while some high expressors do not. Other biomarkers — such as tumor mutational burden (TMB) and microsatellite instability (MSI) — are also used to predict immunotherapy response.