Programmed Death-Ligand 1 (PD-L1) is a protein found on the surface of both healthy cells and some cancer cells. To assess its presence and amount in tumor tissue, a laboratory technique called Immunohistochemistry (IHC) is employed. The PD-L1 IHC test serves as an important tool in cancer care, providing insights into a tumor’s characteristics. This test helps medical professionals understand how a tumor might interact with the body’s immune system.
Understanding PDL1 and Immunohistochemistry
PD-L1, or Programmed Death-Ligand 1, is a protein that regulates the immune system. Normally, PD-L1 acts as a “brake” to prevent immune cells, specifically T cells, from attacking healthy cells in the body. It binds to a receptor called PD-1 on T cells, sending a signal that tells the T cell not to attack. This interaction helps maintain immune balance and prevents autoimmune reactions.
Cancer cells can exploit this natural mechanism by producing high levels of PD-L1 on their surface. When cancer cells express PD-L1, they can bind to PD-1 on T cells, effectively deactivating these immune cells and allowing the tumor to evade detection and destruction by the body’s immune system. This “hijacking” of the immune checkpoint pathway allows cancer cells to grow and spread unchecked.
Immunohistochemistry (IHC) is a laboratory method used to detect specific proteins, such as PD-L1, within tissue samples. The technique relies on the principle of antibodies binding specifically to antigens (proteins) in biological tissues. In IHC, a tissue sample is treated with specially designed antibodies that are engineered to attach only to the PD-L1 protein. These antibodies are often linked to an enzyme or fluorescent dye, which then produces a visible color or light when a substrate is added.
This process allows pathologists to “see” if and where PD-L1 is present on cancer cells or immune cells within a tumor when viewed under a microscope. By combining the understanding of PD-L1’s role in immune evasion with the visualization capabilities of IHC, the test provides valuable information about the tumor’s interaction with the immune system. This combined approach helps in assessing the presence and quantity of PD-L1 in a tumor, which can then guide treatment decisions.
Why PDL1 IHC Matters for Cancer Treatment
The primary purpose of the PD-L1 IHC test is to help determine if a patient’s cancer is likely to respond to a specific class of drugs called immune checkpoint inhibitors. These therapies work by “releasing the brakes” on the immune system, thereby allowing the body’s own T cells to recognize and attack cancer cells. Immune checkpoint inhibitors, such as those targeting PD-1 or PD-L1, have significantly improved outcomes for patients with various types of cancer.
These immunotherapies function by blocking the interaction between PD-L1 on cancer cells (or immune cells within the tumor) and PD-1 on T cells. By disrupting this inhibitory signal, the T cells become reactivated and regain their ability to target and destroy tumor cells. This approach aims to restore the natural anti-tumor immune response that cancer cells often suppress.
PD-L1 expression levels serve as a biomarker, providing guidance for oncologists in making personalized treatment decisions. Higher levels of PD-L1 expression on tumor cells or immune cells within the tumor often indicate a greater likelihood of response to these specific immune checkpoint inhibitors. However, it is also understood that even patients with low or undetectable PD-L1 expression may still benefit from these therapies in some cases, particularly when combined with other treatments.
While PD-L1 expression is a widely validated and used predictive biomarker, it is not the only factor considered. Other elements, such as tumor mutational burden (TMB) and DNA mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H), are also evaluated to provide a comprehensive picture and guide therapeutic strategies. The test helps identify patients who are more likely to respond, optimizing the chances of successful treatment with these targeted immunotherapies.
How the PDL1 IHC Test is Performed
Performing a PD-L1 IHC test begins with obtaining a tissue sample from the patient’s tumor. This is typically done through a biopsy procedure, where a small piece of the tumor is removed. The type of biopsy can vary depending on the tumor’s location and accessibility, ranging from a fine needle aspiration to a core needle biopsy or even a surgical excision.
Once the tissue sample is collected, it undergoes laboratory processing to prepare it for analysis. The tissue is usually preserved, often using formalin fixation, and then embedded in paraffin wax to create a tissue block. This block is then thinly sliced into sections, typically a few micrometers thick, and mounted onto glass slides.
These slides are then subjected to the staining process. Specific antibodies designed to bind to the PD-L1 protein are applied to the tissue sections. After the antibodies bind, a detection system, often involving an enzyme that produces a colored precipitate, is used to visualize the PD-L1 protein under a microscope. Finally, a pathologist, a medical doctor specializing in diagnosing diseases by examining tissues and bodily fluids, examines the stained slides to assess the presence and amount of PD-L1 expression on both tumor cells and tumor-infiltrating immune cells.
Understanding Your PDL1 Test Results
PD-L1 test results are typically reported as a score or a percentage, indicating the level of PD-L1 expression. Two common scoring methods are the Tumor Proportion Score (TPS) and the Combined Positive Score (CPS).
Tumor Proportion Score (TPS)
TPS specifically measures the percentage of viable tumor cells that show partial or complete membrane staining for PD-L1. For example, a TPS of 50% means that half of the tumor cells show PD-L1 expression.
Combined Positive Score (CPS)
The Combined Positive Score (CPS), on the other hand, provides a broader assessment by including PD-L1 staining on tumor cells, lymphocytes, and macrophages, all relative to the total number of viable tumor cells. While a CPS calculation can exceed 100, the maximum reported score is typically defined as CPS 100. A minimum of 100 viable tumor cells on the stained slide is generally required for an adequate evaluation of PD-L1 expression.
A “positive” PD-L1 test result generally means that a sufficient amount of PD-L1 protein is present in the tumor, suggesting that certain immunotherapy medicines, specifically immune checkpoint inhibitors, may be beneficial. Conversely, a “negative” result or low PD-L1 expression indicates that these specific immunotherapies might be less effective. It is important to remember that these results are interpreted by a pathologist and then discussed by the oncology team in the context of the patient’s overall health, the specific type of cancer, and other diagnostic information to determine the most appropriate treatment plan. A low or negative PD-L1 result does not mean that there are no treatment options; rather, it suggests that other therapeutic approaches would likely be considered.