Understanding specific details about a tumor is fundamental to modern cancer care. One molecular signpost is Programmed Death-Ligand 1 (PD-L1), a protein whose presence is quantified by the Tumor Proportion Score (TPS). This measurement is a biomarker that helps predict if a cancer may respond to a specific class of drugs by looking at the level of PD-L1 protein on cancer cells. The score is a percentage, and its value can directly influence the selection of therapies tailored to the biology of a person’s tumor.
The Role of PD-L1 in the Immune System
The immune system has checks and balances to ensure it attacks invaders without harming healthy tissues. The PD-1/PD-L1 pathway is a part of this system. Programmed cell death protein 1 (PD-1) is a receptor on the surface of activated T-cells. Its function is to act as a brake, preventing T-cells from launching an excessive attack.
To signal that a cell is friendly, healthy cells present the PD-L1 protein on their surface. When a T-cell’s PD-1 receptor binds to PD-L1 on a healthy cell, it sends an inhibitory signal to the T-cell, telling it to stand down. This interaction is a mechanism to prevent autoimmune diseases, where the immune system mistakenly attacks the body.
Some cancer cells exploit this protective mechanism to hide from the immune system by producing high levels of PD-L1 on their surfaces. They effectively use the same “off-switch” that healthy cells use. When T-cells primed to attack the cancer encounter PD-L1 on a tumor cell, they receive a “don’t attack” signal. This allows the cancer to evade destruction and continue to grow.
Defining and Measuring the Tumor Proportion Score
The Tumor Proportion Score (TPS) measures the percentage of viable tumor cells that show PD-L1 protein on their surface. To calculate this score, a tumor sample is obtained through a biopsy. A minimum of 100 viable tumor cells is required for the sample to be considered adequate for an accurate evaluation.
In the laboratory, a pathologist uses immunohistochemistry (IHC) to make the PD-L1 protein visible. This process involves applying a specific antibody engineered to bind only to the PD-L1 protein. This antibody is linked to a dye, which stains the cells expressing PD-L1, making them visibly colored under a microscope.
The pathologist then counts the number of stained tumor cells and compares it to the total number of viable tumor cells in the sample. For instance, if 60 out of 100 tumor cells are stained for PD-L1, the TPS is 60%. This score provides a standardized way to report the level of PD-L1 expression.
How PD-L1 TPS Guides Cancer Treatment
The PD-L1 TPS is a predictive biomarker that helps forecast how a cancer might respond to immune checkpoint inhibitors. These therapies block the interaction between the PD-1 receptor on T-cells and the PD-L1 protein on tumor cells. By disrupting this connection, the drugs “release the brakes” on the immune system, allowing T-cells to recognize and attack the cancer.
The clinical utility of TPS uses specific cutoff points, which vary by cancer type and the drug being considered. For Non-Small Cell Lung Cancer (NSCLC), these thresholds are well-defined. A TPS of less than 1% is considered PD-L1 negative, and immunotherapy is less likely to be recommended as a first-line standalone treatment in these cases.
When the score is 1% or higher, the tumor is considered PD-L1 positive. A TPS between 1% and 49% may make a patient eligible for an immune checkpoint inhibitor, often combined with chemotherapy. A score of 50% or greater is classified as high PD-L1 expression, and an immune checkpoint inhibitor may be recommended as a standalone first-line treatment, known as monotherapy.
For example, the drug pembrolizumab may be used as a single agent for metastatic NSCLC if the TPS is 1% or greater and the disease has progressed after chemotherapy. For patients with a high expression level (TPS ≥50%), it may be used as an initial treatment instead of chemotherapy. These guidelines are based on clinical trials showing improved survival in patients with higher PD-L1 expression.
Limitations and Other Biomarker Considerations
The Tumor Proportion Score is not a perfect predictor of treatment success. Some patients with a high TPS may not respond to immunotherapy, while a few with a low or negative TPS may still benefit. This variability shows that other biological factors are also at play in the tumor’s interaction with the immune system.
To capture a more complete picture, scientists developed other scoring methods like the Combined Positive Score (CPS). Unlike TPS, which only counts PD-L1-positive tumor cells, CPS also includes PD-L1-positive immune cells like lymphocytes and macrophages. This broader measurement is used to guide immunotherapy decisions in other cancers, such as gastric, head and neck, and cervical cancers.
The choice between using TPS or CPS depends on the cancer type and the specific drug. For instance, CPS is the preferred metric for pembrolizumab in certain gastric cancers. An oncologist will consider the PD-L1 score alongside other information, like the cancer’s stage and the patient’s overall health, to develop a treatment plan.