Being “PD-L1 positive” in the context of cancer means that cancer cells have a specific protein called Programmed Death-Ligand 1 (PD-L1) on their surface. This protein plays a role in the body’s immune system, and its presence on tumor cells carries significant implications for how the cancer interacts with the immune system. Identifying PD-L1 positivity helps doctors understand certain characteristics of the tumor and can guide treatment decisions.
How PD-1 and PD-L1 Interact
The body’s immune system uses a complex network of checks and balances to distinguish between healthy cells and harmful invaders or diseased cells. Among these are immune checkpoints, which are like “brakes” that prevent the immune system from overreacting and attacking healthy tissues.
One such checkpoint involves two proteins: PD-1 and PD-L1. PD-1 (Programmed Death-1) is found on the surface of immune cells, specifically T-cells, which are the immune system’s primary fighters against diseased cells. PD-L1 is a protein that can be found on various cells throughout the body, including some healthy cells.
When PD-1 on a T-cell binds to PD-L1 on another cell, it sends an inhibitory signal to the T-cell, telling it not to attack. This interaction is a natural mechanism to maintain immune tolerance and prevent the immune system from mistakenly targeting healthy cells. This binding helps regulate the immune response.
Why PD-L1 Positivity Matters in Cancer
Cancer cells are abnormal and should be recognized and destroyed by the immune system. However, many cancer cells have developed ways to evade immune detection and destruction. One common method involves exploiting the normal PD-1/PD-L1 pathway.
Cancer cells can produce and display PD-L1 on their surface. When these PD-L1-expressing cancer cells encounter PD-1-carrying T-cells, the PD-L1 acts like an “off switch.” This binding deactivates the T-cell, preventing it from recognizing and attacking the cancer.
This mechanism allows the tumor to evade the immune system. When a tumor is “PD-L1 positive,” it indicates that the cancer cells are using this immune evasion strategy.
Determining PD-L1 Status
Determining a patient’s PD-L1 status begins with obtaining a tissue sample from the tumor. This is done through a biopsy, where a small piece of the cancerous tissue is removed. The tissue sample is then sent to a specialized laboratory for analysis.
In the lab, a technique called immunohistochemistry (IHC) is used to detect and measure the amount of PD-L1 protein present on the surface of the cancer cells. This method uses specific antibodies that bind to the PD-L1 protein, making it visible under a microscope. The results are expressed as a percentage, indicating the proportion of tumor cells that express PD-L1, or as a score.
Two common scoring systems are the Tumor Proportion Score (TPS) and the Combined Positive Score (CPS). TPS measures the percentage of viable tumor cells with partial or complete membrane staining for PD-L1. CPS considers PD-L1 expression on tumor cells, as well as on tumor-infiltrating immune cells like lymphocytes and macrophages, providing a broader assessment of PD-L1 expression within the tumor microenvironment.
PD-L1 and Immunotherapy Options
Knowing a tumor’s PD-L1 status is a factor in guiding cancer treatment, particularly for a class of drugs known as immune checkpoint inhibitors. These therapies work by targeting the PD-1/PD-L1 pathway to restore the immune system’s ability to fight cancer.
Drugs such as pembrolizumab, nivolumab, atezolizumab, durvalumab, avelumab, and cemiplimab are examples of immune checkpoint inhibitors. These medications are designed to block the interaction between PD-1 on T-cells and PD-L1 on cancer cells. By preventing this binding, these inhibitors “release the brakes” on the immune system, allowing T-cells to become active again and destroy the cancer cells.
PD-L1 positivity in a tumor predicts a higher likelihood of response to these specific immunotherapies. This is because the presence of PD-L1 on tumor cells indicates that the cancer is actively using this pathway to evade the immune system, making it a suitable target for these blocking agents. The development of anti-PD-1/PD-L1 inhibitors has improved patient outcomes in various cancers, including non-small cell lung cancer and melanoma.
Interpreting PD-L1 Test Results
While PD-L1 positivity suggests a patient may respond well to certain immunotherapies, interpreting the test results involves several considerations. A positive result does not guarantee a response, nor does a low or negative result rule out benefit. Different cancer types and specific immunotherapy drugs may have varying PD-L1 positivity thresholds for treatment eligibility.
For example, in non-small cell lung cancer, a Tumor Proportion Score (TPS) of 1% or higher might indicate eligibility for some immunotherapies, while a TPS of 50% or higher might suggest monotherapy as a first-line option. The Combined Positive Score (CPS) is used for other cancer types, such as gastric or cervical cancer, where different thresholds, like CPS ≥1 or CPS ≥10, may apply.
Some patients with “low” or “negative” PD-L1 expression may still benefit from immunotherapy, especially when these drugs are used in combination with other treatments like chemotherapy. PD-L1 status is one piece of a larger puzzle. Doctors consider the PD-L1 test results alongside other factors, including the specific type and stage of cancer, other genetic markers, and the patient’s overall health and previous treatments, to formulate a treatment plan.