PD-L1 IHC is a specialized laboratory test that functions as a predictive biomarker for immunotherapy, a class of cancer drugs. This test provides insight into whether a patient’s tumor is using a particular mechanism to hide from the immune system, which has the natural ability to eliminate cancerous cells.
The results help oncologists tailor treatment to an individual’s specific cancer biology. It is not a test that diagnoses cancer, but one that characterizes an already diagnosed tumor. By identifying certain proteins on cancer cells, the test helps predict if treatments designed to reactivate the immune system will be successful, moving away from a one-size-fits-all model.
The PD-1/PD-L1 Immune Checkpoint
The immune system has powerful T-cells that can recognize and destroy cancer cells. To prevent these T-cells from attacking healthy tissues, the body uses regulatory pathways called immune checkpoints. These checkpoints act as natural brakes, ensuring the immune response remains controlled and does not cause autoimmune disease.
One checkpoint involves the Programmed Death-1 (PD-1) receptor on T-cells. When activated, PD-1 inhibits the T-cell, effectively telling it to stand down. Normal cells have a protein called Programmed Death-Ligand 1 (PD-L1), and its interaction with PD-1 is a normal way the body maintains immune balance.
Some cancer cells exploit this system by expressing high levels of PD-L1 on their surface. When a T-cell’s PD-1 receptor binds to the PD-L1 on a cancer cell, the T-cell receives an “off” signal. This interaction allows the cancer to camouflage itself, creating a form of adaptive immune resistance to evade destruction.
The PD-L1 IHC Testing Process
Testing for PD-L1 expression begins with a tissue sample from the patient’s tumor, collected via a biopsy or from a specimen removed during surgery. The tissue is carefully preserved to maintain its cellular structure and protein integrity.
In the lab, the tissue is embedded in wax, sliced into thin sections, and mounted on microscope slides. The immunohistochemistry (IHC) procedure then begins. This technique uses specially engineered antibodies that recognize and bind to the PD-L1 protein on the tissue sample.
These antibodies are linked to an enzyme that activates a dye, creating a visible color where the PD-L1 protein is present. This staining process makes the protein’s presence on the cell surface visible under a microscope.
A pathologist, a doctor specializing in examining tissues to diagnose disease, then analyzes these prepared slides. They examine the stained cells to determine the extent and intensity of PD-L1 expression. This analysis generates the test result used to inform treatment decisions.
Understanding PD-L1 Expression Scores
The pathologist’s observations are translated into a quantitative score measuring the level of PD-L1 expression. Two primary scoring systems are used, and the choice often depends on the cancer type and the specific immunotherapy drug being considered.
The first metric is the Tumor Proportion Score (TPS). This score is the percentage of viable tumor cells showing PD-L1 staining relative to all viable tumor cells. For example, if a pathologist counts 100 tumor cells and finds that 40 of them are stained for PD-L1, the TPS would be reported as 40%.
Another metric is the Combined Positive Score (CPS). The CPS is more inclusive, accounting for PD-L1 staining on both tumor cells and certain immune cells like lymphocytes and macrophages. It is calculated by dividing the total number of PD-L1 stained cells by the total number of viable tumor cells, then multiplying by 100.
The scoring method used is specific to the cancer type. For instance, TPS is often used for non-small cell lung cancer, while CPS is the standard for head and neck squamous cell carcinoma and urothelial carcinoma. These scores provide a standardized way to interpret results for treatment guidelines.
Guiding Immunotherapy Treatment
The PD-L1 score predicts a patient’s response to immune checkpoint inhibitors. These drugs block the PD-1/PD-L1 interaction, allowing T-cells to recognize and attack the cancer.
The TPS or CPS score directly influences treatment by establishing cutoffs for therapy. For example, a patient with a high TPS (e.g., 50% or greater) might be a candidate for immunotherapy alone as a first-line therapy. A patient with a lower score might be recommended a combination of immunotherapy and chemotherapy.
The FDA has approved specific PD-L1 IHC assays as companion diagnostics for certain drugs. This means the test is required to determine eligibility for that treatment. This link between the biomarker score and drug selection is a cornerstone of personalized cancer therapy.
Nuances in PD-L1 Testing
While PD-L1 IHC testing is a valuable tool, it has several complexities:
- Tumor heterogeneity: PD-L1 expression can vary widely across different areas of a single tumor or between a primary tumor and its metastatic sites. A biopsy is only a small sample, and its score might not represent the entire cancer burden.
- Assay variability: Several different PD-L1 IHC assays exist, each using a unique antibody like 22C3 or 28-8. These assays are often developed alongside specific drugs and can have different performance characteristics or scoring systems.
- Dynamic expression: The expression of PD-L1 is not static and can change over time or in response to treatments like chemotherapy or radiation. A result from an initial biopsy may not reflect the tumor’s status later in the disease.
- Imperfect prediction: The test is not a perfect predictor of who will benefit. Some patients with low PD-L1 scores still respond to immune checkpoint inhibitors, while some with high scores do not, indicating other factors are involved.