The Programmed Death-Ligand 1 Tumor Proportion Score, or PD-L1 TPS, is a diagnostic measurement used in the field of cancer treatment. This score quantifies the amount of a specific protein, PD-L1, present on the surface of cancer cells in a patient’s tumor sample. Determining the PD-L1 TPS is a routine and necessary step for doctors considering certain modern therapies for cancer. The result provides a numerical value that helps predict how likely a patient is to respond to a type of drug known as an immune checkpoint inhibitor. This measurement guides oncologists in tailoring the most effective treatment strategy for individuals, particularly those with Non-Small Cell Lung Cancer.
The Role of PD-L1 in Immune Evasion
The body’s immune system naturally uses a series of checkpoints to prevent T-cells from attacking healthy tissues, similar to a regulatory brake system. Cancer cells exploit this normal biological process by expressing the PD-L1 protein on their surface. This protein acts like a cloak, engaging with a corresponding receptor called PD-1 found on the surface of active T-cells.
The interaction between PD-L1 on the tumor cell and PD-1 on the T-cell sends an inhibitory signal to the T-cell. This signal effectively tells the immune cell to stand down and not attack the cancer. By activating this pathway, the tumor successfully evades detection and destruction by the host’s immune system, a process known as immune evasion.
High levels of PD-L1 expression on tumor cells suggest that this cloaking mechanism is strongly engaged. Immunotherapy drugs, called checkpoint inhibitors, work by blocking this PD-1/PD-L1 interaction. By releasing the “brake,” these drugs allow the T-cells to recognize and attack the cancer. The PD-L1 TPS is therefore a direct measure of the target that these specific drugs are designed to neutralize.
How the Tumor Proportion Score is Calculated
The Tumor Proportion Score is a specific, quantitative measure expressed as a percentage, ranging from 0% to 100%. Pathologists calculate the TPS by counting the number of viable tumor cells that show partial or complete membrane staining for the PD-L1 protein. This count is then divided by the total number of all viable tumor cells present in the sample.
The TPS method focuses exclusively on the cancer cells themselves. The calculation deliberately excludes any PD-L1 staining found on surrounding immune cells, such as lymphocytes or macrophages, in the tumor microenvironment. This is a key distinction from other scoring methods, like the Combined Positive Score, which incorporates immune cell staining into its final number.
To ensure the reliability of the result, pathologists must analyze a minimum of 100 viable tumor cells in the stained tissue sample. Any visible staining, even faint or partial, on the cell membrane is counted as positive for the PD-L1 protein. The resulting percentage directly reflects the proportion of the tumor mass that is actively using the PD-L1 protein to hide from the immune system.
The Procedure for PD-L1 TPS Testing
The process begins with obtaining a small sample of the patient’s tumor tissue, typically through a biopsy or a surgical procedure. This tissue sample must be preserved using a standard technique, which involves fixing it in formalin and embedding it in a paraffin wax block. This formalin-fixed, paraffin-embedded (FFPE) tissue block is then sent to a specialized laboratory for testing.
In the laboratory, thin slices of the tissue are placed on glass slides and subjected to a technique called immunohistochemistry (IHC). This process uses a specific, pre-approved antibody “clone,” such as the 22C3 clone, designed to bind only to the PD-L1 protein. Once the antibody binds, a chemical reaction stains the protein, making it visible under a microscope.
A trained pathologist then manually examines the stained slide to determine the TPS. The pathologist systematically counts the total number of viable tumor cells and the number of those cells showing the distinct membrane staining. The final TPS percentage is reported, and the accuracy of this score relies heavily on the quality of the original tissue sample and the pathologist’s expertise in interpreting the staining pattern.
Connecting TPS Results to Immunotherapy Decisions
The numerical TPS result is directly linked to the probability of a patient responding to a specific anti-PD-1 or anti-PD-L1 immunotherapy drug. This scoring system is predominantly used to guide treatment decisions in Non-Small Cell Lung Cancer (NSCLC), where it has become a standard predictive biomarker. Clinical guidelines establish distinct thresholds that determine the appropriate treatment path, whether it be monotherapy, combination therapy, or chemotherapy alone.
Low Expression (TPS < 1%)
A TPS of less than 1% is generally considered to be low or negative PD-L1 expression. For patients in this category, single-agent immunotherapy is typically not recommended as a first-line treatment option because the immune evasion mechanism is less pronounced. Instead, these patients are often treated with traditional chemotherapy or a combination approach involving chemotherapy plus an immune checkpoint inhibitor.
Intermediate Expression (TPS 1%–49%)
Tumors with an intermediate TPS, defined as a score between 1% and 49%, show a measurable level of PD-L1 expression. This level indicates that the patient may be eligible for certain combination therapies, such as chemotherapy paired with immunotherapy. For some patients, a score of 1% or greater qualifies them for second-line monotherapy, meaning the immune checkpoint inhibitor is used after a first-line treatment has failed.
High Expression (TPS ≥ 50%)
The highest likelihood of response to monotherapy is observed in patients whose tumors have a TPS of 50% or greater. This high expression level suggests that the PD-L1 cloaking mechanism is very active, making it an excellent target for blocking drugs. In this high-positive group, a single-agent checkpoint inhibitor, such as pembrolizumab, is often recommended as the first-line treatment, as it has shown superior outcomes compared to chemotherapy alone in this patient population.