What a PD-L1 Score Means for Immunotherapy

This page is for people whose pathology report includes a PD-L1 score. It explains the three scoring systems, why cutoffs differ, and why the score is only part of the picture.

PD-L1 is a protein that acts as a brake. When it sits on the surface of a tumor cell and meets PD-1 on an immune T cell (a white blood cell that attacks threats), the T cell stands down. NCI says some tumors make extra PD-L1, which helps them hide from the immune system.

Checkpoint inhibitor drugs block that handshake and release the brake. Pembrolizumab, nivolumab and atezolizumab are examples. Testing for PD-L1 tries to work out, in advance, whose cancer relies on this particular brake.

Your pathology report will use one of three systems. They are not interchangeable.

TPS, the tumor proportion score, counts only cancer cells: the percentage showing PD-L1 staining on their surface. It is used mainly in non-small cell lung cancer.

CPS, the combined positive score, counts PD-L1-positive cells of three types: tumor cells, lymphocytes, and macrophages (two kinds of immune cells). That count is divided by the total number of tumor cells, then multiplied by 100. CPS is used in gastric, esophageal, cervical, head and neck and triple-negative breast cancers. Immune cells are counted on top of that fraction but not on the bottom. Because of that, the result can go above 100. When it does, it is capped at 100. A CPS is a number, not a percentage.

IC, the immune cell score, measures something different. It looks at the tumor area and asks what share of it is taken up by PD-L1-positive immune cells. It is used with atezolizumab, and the cutoff differs by cancer: IC of 5% or above in urothelial (bladder) cancer, IC of 1% or above in triple-negative breast cancer.

There is no single PD-L1 threshold. Each one was set in the trial that led to that approval.

• Non-small cell lung cancer: a TPS of 50% or above supports pembrolizumab used alone. The FDA later expanded that approval. Now a TPS of 1% or above also qualifies, using the 22C3 test.
• Triple-negative breast cancer: a CPS of 10 or above supports pembrolizumab plus chemotherapy.
• Head and neck cancer: a CPS of 1 or above supports pembrolizumab used on its own as first-line (first) treatment. Pembrolizumab combined with platinum and fluorouracil is approved there without any PD-L1 requirement.
• Gastric and esophageal cancers: the CPS threshold is 1 or 10, depending on the cancer and the regimen used.
• Cervical cancer: a CPS of 1 or above is used.

The antibody used for the test matters too. Four versions (clones) dominate: 22C3, 28-8, SP263 and SP142. Each was developed alongside a particular drug. They do not give identical results on identical tissue. SP142 in particular tends to score lower than the others. Because of this, a score from one test (assay) cannot be read across to a drug that was validated with a different one.

PD-L1 is one of the better biomarkers available. It is still far from decisive.

A biopsy is a sample from one place at one moment, so a PD-L1 result describes that sample. The test is also sensitive to which antibody is used: in one comparison of three FDA-approved assays, only about 60% of samples gave consistent results across all three.

The practical consequence is that a score is one piece of information. If your score came back low, ask your team what it means for your options.

PD-L1 is usually interpreted alongside other results. The FDA label for pembrolizumab also lists mismatch repair deficiency or high microsatellite instability (dMMR/MSI-H) and high tumor mutational burden (TMB-H) as separate markers. The FDA's first-line lung cancer approval for pembrolizumab applies to tumors with no EGFR or ALK changes. Ask your team which results apply to you.

Some immunotherapy uses are approved without any PD-L1 requirement. For those, the score does not decide who qualifies.

A PD-L1 score is a statement about likelihood. It comes from a specific test, for a specific drug, in a specific cancer. It is worth knowing which assay produced your result. It is worth knowing which cutoff applies to your case. Those two details determine what the number actually means for your options.

• FDA — PD-L1 IHC 22C3 pharmDx (TPS and CPS scoring)
• FDA — Ventana PD-L1 SP142 Assay (IC scoring)
• Maule et al. 2022 (PMC) — PD-L1 antibody clone comparison
• FDA — Pembrolizumab for HER2-positive gastric/GEJ adenocarcinoma expressing PD-L1 (CPS ≥1)
• FDA — KEYTRUDA (pembrolizumab) prescribing information (CPS cutoffs by indication)
• NCI — Immune Checkpoint Inhibitors
• NCI Dictionary — PD-L1