The Tumor Proportion Score (TPS) is a standardized measurement used in oncology to determine which patients are most likely to benefit from immunotherapy. It functions as a predictive diagnostic tool, quantifying the presence of the PD-L1 biological marker on the surface of cancer cells. The TPS result is expressed as a percentage, providing oncologists with a numerical value to guide personalized treatment selection. This score is derived from laboratory analysis of a patient’s tumor tissue and is integral to the decision-making process for certain advanced cancers.
The Biological Basis of PD-L1 Expression
The TPS measures the expression of the protein Programmed Death-Ligand 1 (PD-L1), which allows cancer cells to evade the body’s immune system. PD-L1 is a surface protein that binds to its receptor, PD-1, which is found on T-cells, a type of immune cell responsible for killing abnormal cells. This binding interaction essentially delivers an “off” signal to the T-cell, preventing it from recognizing and attacking the cancer cell. Cancer cells exploit this natural immune checkpoint pathway to protect themselves and continue growing unchecked.
Immunotherapy drugs known as checkpoint inhibitors are designed to block this inhibitory interaction. These drugs target either the PD-L1 protein on the tumor cell or the PD-1 receptor on the T-cell, effectively disconnecting the “off” switch. By interrupting the PD-1/PD-L1 pathway, the therapy releases the brakes on the immune system, allowing T-cells to become active and mount an effective anti-tumor response. Measuring the amount of PD-L1 on the tumor surface gives a direct indication of how much the cancer is relying on this evasion strategy, which correlates with the potential effectiveness of blocking it.
Determining the Tumor Proportion Score
Pathologists calculate the Tumor Proportion Score through a laboratory technique called immunohistochemistry (IHC). This technique uses specialized antibodies to visually tag the PD-L1 protein in a tumor tissue sample. A small tissue sample, typically from a biopsy or surgical resection, is stained with a colored reagent that binds only to the PD-L1 protein. Any cancer cell membrane that displays PD-L1 will show a visible stain, allowing the pathologist to count it.
The score is a ratio expressed as a percentage, reflecting the proportion of viable tumor cells that exhibit partial or complete membrane staining for PD-L1. The formula is the number of PD-L1-positive tumor cells divided by the total number of viable tumor cells, multiplied by 100. Testing requires the tissue specimen to contain a minimum of 100 viable tumor cells. The pathologist must specifically count only the tumor cells and exclude surrounding cells, such as immune cells and stromal cells, from the TPS calculation.
Clinical Interpretation of TPS Results
The numerical TPS result directly influences the selection of immunotherapy treatment, particularly for cancers like non-small cell lung cancer (NSCLC). A high TPS score generally suggests that the tumor is heavily using the PD-L1 pathway to hide from the immune system, indicating a higher probability that blocking this pathway will be effective. Conversely, a low score suggests the tumor may be using other mechanisms of immune evasion, making combination therapy or alternative treatments more appropriate.
Clinical guidelines often divide TPS results into three major categories to guide treatment decisions. A TPS of less than 1% is considered “PD-L1 negative” and suggests that immunotherapy monotherapy is less likely to be effective. This patient group is often considered for chemotherapy alone or chemotherapy combined with immunotherapy. A TPS in the range of 1% to 49% is considered “low expression” and may qualify patients for certain immunotherapy drugs, sometimes in combination with traditional chemotherapy.
The most favorable category for single-agent immunotherapy is a TPS of 50% or greater, defined as “high expression.” Patients with this high score have demonstrated a higher likelihood of significant response to immunotherapy alone in the first-line setting. These threshold categories correlate directly with the specific inclusion criteria established during the clinical trials that led to the approval of various immunotherapy drugs.
Variables Affecting TPS Accuracy
Assay Variability
The accuracy of the Tumor Proportion Score can be affected by several variables, which introduce complexity into the testing process. One factor is the choice of the testing assay, as different drug manufacturers developed unique diagnostic tests that use distinct antibody clones, such as 22C3, 28-8, and SP142. While some assays show comparable results, others, like the SP142 assay, have been shown to stain fewer tumor cells, potentially leading to a lower TPS result for the same tumor sample.
Sample Quality and Interpretation
The quality and type of the tissue sample also play a substantial role. Small biopsy samples or archived tissue specimens may not fully capture the spatial heterogeneity of PD-L1 expression, which can vary across different regions of a single tumor. Furthermore, there is a risk of inter-observer variability, where different pathologists may arrive at slightly different scores, particularly for results that fall near the clinically significant thresholds of 1% or 50%. Pathologists require specific training to minimize interpretation issues and ensure consistency in scoring.