Programmed death-ligand 1 (PD-L1) is a protein found on the surface of some cells, including certain cancer cells. This protein interacts with another protein called PD-1, located on immune cells known as T-cells. Normally, this interaction helps regulate the immune system, preventing it from attacking healthy tissues. However, cancer cells can exploit this pathway by expressing PD-L1, effectively “hiding” from the immune system and allowing the tumor to grow and spread. Measuring PD-L1 expression on tumor cells helps determine how likely a cancer might respond to treatments targeting this immune evasion, and the Tumor Proportion Score (TPS) quantifies this expression.
Understanding PD-L1 Tumor Proportion Score
The Tumor Proportion Score (TPS) measures PD-L1 expression by calculating the percentage of viable tumor cells showing PD-L1 staining on their surface. This score ranges from 0% to 100%. A higher TPS indicates more tumor cells expressing PD-L1, suggesting the tumor actively evades the immune response.
PD-L1 expression on tumor cells is significant for immune evasion. When PD-L1 on a tumor cell binds to PD-1 on a T-cell, it sends an inhibitory signal that deactivates the T-cell, preventing it from recognizing and destroying the cancer cell. This interaction essentially puts a “brake” on the immune system’s anti-tumor activity. Understanding the percentage of tumor cells expressing PD-L1 helps clinicians gain insight into how effectively the cancer suppresses the immune response.
How PD-L1 Tumor Proportion Score is Assessed
Determining a patient’s PD-L1 Tumor Proportion Score (TPS) begins with a tumor tissue sample, typically from a biopsy. This tissue is then prepared and embedded in paraffin to create a formalin-fixed, paraffin-embedded (FFPE) block. A minimum of 100 viable tumor cells are generally required in the tissue specimen for evaluation.
The laboratory technique used to detect PD-L1 protein in the tissue sample is called immunohistochemistry (IHC). This method involves applying specific antibodies that bind to the PD-L1 protein, causing the cells expressing it to stain a particular color. Different antibody clones, such as 22C3, SP263, and SP142, are used for PD-L1 IHC, with 22C3 being a commonly approved clone for certain cancer types like non-small cell lung cancer (NSCLC).
A pathologist then examines the stained tissue sample under a microscope. The pathologist counts viable tumor cells showing partial or complete membrane staining for PD-L1 and divides this by the total viable tumor cells. This yields the Tumor Proportion Score.
Interpreting PD-L1 Tumor Proportion Score Results and Treatment Guidance
Interpreting PD-L1 Tumor Proportion Score (TPS) results directly influences cancer treatment decisions, particularly for immunotherapies. Different TPS percentages guide oncologists in selecting appropriate therapies, as a higher TPS correlates with a greater likelihood of response to certain immune checkpoint inhibitors. For example, in non-small cell lung cancer (NSCLC), a TPS of less than 1% typically indicates very low or no PD-L1 expression. A TPS between 1% and 49% signifies low expression, and 50% or greater denotes high expression.
These different TPS categories often correspond to distinct treatment pathways. For instance, patients with NSCLC showing a high TPS (≥50%) may be candidates for monotherapy with an immune checkpoint inhibitor, such as pembrolizumab, as a first-line treatment. This approach aims to “release the brakes” on the immune system, allowing T-cells to recognize and attack the cancer. In contrast, for patients with a lower TPS (e.g., 1-49%), a combination of immunotherapy with chemotherapy might be considered, or immunotherapy could be used as a second-line treatment after initial chemotherapy.
TPS is one of several factors oncologists consider when developing a treatment plan. Other considerations include the specific type and stage of cancer, the patient’s overall health, and the presence of other genetic mutations in the tumor, such as EGFR or ALK aberrations in NSCLC. While a high TPS suggests a greater chance of response to certain immunotherapies, some patients with lower or even negative TPS scores may still benefit from these treatments, especially when used in combination with other therapies. The specific cut-off points for TPS can also vary depending on the cancer type and the immune checkpoint inhibitor.