From the Guidelines
PD-L1 level is considered positive when the combined positive score (CPS) is ≥ 1, which correlates with a clinical benefit to programmed cell death protein-1 (PD-1) inhibitors. PD-L1 level refers to the amount of programmed death-ligand 1 protein expressed on the surface of cells, particularly cancer cells. This protein is measured as part of cancer diagnosis and treatment planning because it helps predict how well a patient might respond to immunotherapy treatments called checkpoint inhibitors. PD-L1 works by binding to PD-1 receptors on immune cells, which essentially tells the immune system not to attack those cells. Cancer cells often exploit this mechanism by overexpressing PD-L1 to evade immune detection. The level is typically reported as a percentage of cells expressing the protein or as high/low expression. Higher PD-L1 levels generally indicate a greater likelihood of response to anti-PD-1/PD-L1 immunotherapies like pembrolizumab, nivolumab, or atezolizumab. Testing for PD-L1 is done through immunohistochemistry on tissue samples obtained from biopsies. Different cancer types have different thresholds for what's considered a significant PD-L1 level, so interpretation depends on the specific cancer being treated 1.
Some key points to consider when interpreting PD-L1 levels include:
- The CPS is a measure of the number of PD-L1 staining cells of all types divided by the total viable tumor cells and multiplied by 100.
- A CPS of ≥ 1 is considered positive and correlates with a clinical benefit to PD-1 inhibitors.
- PD-L1 expression levels are not an ideal biomarker because some patients with low PD-L1 expression levels respond to immunotherapy and others with high levels do not respond to immunotherapy.
- Tumor mutational burden (TMB) is another biomarker that has been assessed in clinical trials to see if it is useful for predicting whether patients with metastatic NSCLC will respond to various immunotherapy regimens.
It's also important to note that the interpretation of PD-L1 levels can vary depending on the specific cancer type and the treatment being considered. For example, in non-small cell lung cancer, a PD-L1 level of ≥ 50% is considered high and is associated with a higher response rate to single-agent immunotherapy 1. However, in other cancer types, such as head and neck cancer, a CPS of ≥ 1 is considered positive and correlates with a clinical benefit to PD-1 inhibitors 1.
In summary, PD-L1 level is an important biomarker in cancer treatment, and a CPS of ≥ 1 is considered positive and correlates with a clinical benefit to PD-1 inhibitors. However, the interpretation of PD-L1 levels can vary depending on the specific cancer type and the treatment being considered, and other biomarkers such as TMB may also be useful in predicting response to immunotherapy.
From the Research
Definition of PD-L1 Level
- PD-L1 (Programmed Death-Ligand 1) is a protein expressed on the surface of tumor cells that can bind to PD-1 (Programmed Cell Death-1) on T cells, inhibiting T-cell responses and promoting immune evasion 2, 3, 4.
- The level of PD-L1 expression can vary among different types of cancer and even within the same tumor, influencing the effectiveness of immunotherapies targeting the PD-1/PD-L1 axis 3, 5.
Clinical Significance of PD-L1 Level
- PD-L1 expression is generally associated with poorer prognosis in various malignancies, but it can also serve as a predictive biomarker of response to anti-PD-1/PD-L1 therapies 3, 6.
- The level of PD-L1 expression can guide the selection of immunotherapy methods, with different treatments showing better survival rates in patients with specific PD-L1 expression levels 6.
PD-L1 Expression Levels and Immunotherapy
- Patients with high PD-L1 expression (≥50%) may benefit from platinum-based chemotherapy plus pembrolizumab/atezolizumab or pembrolizumab/cemiplimab monotherapy 6.
- Those with low PD-L1 expression (<1%) may benefit from platinum-based chemotherapy plus pembrolizumab or nivolumab and ipilimumab 6.
- Patients with intermediate PD-L1 expression (1-49%) may benefit from platinum-based chemotherapy plus pembrolizumab 6.