Programmed Death-Ligand 1 (PD-L1) testing represents a method to personalize treatment planning for cancer patients, particularly those considered for certain advanced therapies. This testing focuses on identifying a specific protein biomarker on the surface of tumor cells. The result is quantified using the Tumor Proportion Score (TPS), a standardized numerical measurement. The TPS is a percentage that helps oncologists determine the likelihood that a patient’s tumor will respond to immune checkpoint inhibitors. This diagnostic step ensures that targeted treatments are directed toward the patients who stand to benefit the most.
The Biological Role of PD-L1
PD-L1 is a protein that resides on the surface of various cells throughout the body, including many cancer cells. Its biological function is to interact with a receptor protein called PD-1, which is found on the surface of immune cells, specifically T-cells. This interaction forms an immune checkpoint, part of the body’s natural regulatory system. Under normal circumstances, the binding of PD-L1 to PD-1 helps to prevent the immune system from mistakenly attacking healthy tissues, maintaining immune tolerance.
Cancer cells exploit this natural biological pathway for survival by significantly increasing PD-L1 expression on their surface. When a cancer cell’s PD-L1 binds to a T-cell’s PD-1, it sends an inhibitory signal. This acts like a “stop” signal, preventing the T-cell from recognizing and destroying the tumor.
This mechanism allows the cancer to evade detection by the immune system, promoting tumor growth. The goal of modern immunotherapy is to disrupt this inhibitory interaction. By blocking the binding of PD-L1 to PD-1 using specialized drugs, the “brake” is released, allowing the T-cells to reactivate and mount an effective anti-tumor response.
Understanding the Tumor Proportion Score
The Tumor Proportion Score (TPS) is the method used to quantify the level of PD-L1 protein on tumor cells, providing a numerical value for this biomarker. This measurement is performed using Immunohistochemistry (IHC) on a tissue sample, typically obtained through a biopsy. The tissue sample is stained with a specialized antibody that specifically binds to the PD-L1 protein, making its presence visible under a microscope.
The TPS is defined as the percentage of viable tumor cells that show partial or complete membrane staining for the PD-L1 protein. A pathologist calculates this number by visually counting the PD-L1-positive tumor cells and dividing it by the total number of viable tumor cells in the analyzed area. The process requires careful morphological assessment to distinguish tumor cells from surrounding normal or immune cells.
For example, a TPS of 50% indicates that half of the total tumor cells in the analyzed sample are expressing the PD-L1 protein. The TPS method only counts the tumor cells themselves, distinguishing it from other scoring systems like the Combined Positive Score (CPS), which also includes surrounding immune cells in its calculation.
Interpreting Results and Guiding Immunotherapy
The Tumor Proportion Score directly influences the selection of cancer treatment, particularly for anti-PD-1 or anti-PD-L1 immunotherapies. Oncologists divide the TPS results into categories that correspond to differing probabilities of therapeutic response. This stratification helps to match the right patient with the right treatment strategy.
Low Expression (TPS < 1%)
A result showing a TPS of less than 1% is generally considered PD-L1 negative. Patients with a tumor in this category are less likely to experience a significant benefit from receiving immunotherapy as a monotherapy. For these patients, initial treatment often involves traditional chemotherapy or a combination approach that may integrate immunotherapy with other drug classes.
Intermediate Expression (TPS 1%–49%)
Tumors with a TPS ranging from 1% to 49% fall into the low or intermediate positive category. This range suggests the immune pathway is active enough to potentially respond to treatment, though often not as robustly as tumors with higher expression. For this group, combination therapy, such as immunotherapy administered alongside chemotherapy, has become a standard approach in many cancer types, including NSCLC.
High Expression (TPS ≥ 50%)
The most favorable result for single-agent immunotherapy is a TPS of 50% or greater, classified as high positive PD-L1 expression. A score in this upper range strongly correlates with a high likelihood of a positive and durable response to immunotherapy monotherapy as a first-line treatment. This high TPS value indicates that the cancer is heavily relying on the PD-L1 pathway to suppress the immune system, making it an excellent target for treatment. Although the TPS is a powerful predictor, the final treatment decision always incorporates other factors, including the specific type of cancer, the stage of the disease, and the patient’s overall health status.